nan
Predictive evidence:
Predictive: The study evaluates whether mutation status of k-ras, b-raf, or p53 could predict which patients were more likely to respond to bevacizumab, indicating a focus on the relationship between these variants and treatment response. The mention of hazard ratios for death among patients with different mutation statuses further supports this classification as it relates to therapy outcomes.
nan
nan evidence:
Missing abstract
nan
Predictive, Prognostic evidence:
Prognostic: The study indicates that the BRAF V600E mutation is associated with a significantly higher likelihood of disease progression and death, marking it as a poor prognostic factor independent of treatment regimen. This is supported by the reported hazard ratios for early relapse and death, demonstrating its impact on patient outcomes.
Predictive: The BRAF V600E mutation is mentioned as a predictor for early relapse on first-line therapy, suggesting that it correlates with treatment response. The study discusses the implications of this mutation for patient selection and stratification in clinical trials, indicating its relevance in predicting therapy outcomes.
nan
Predictive, Prognostic evidence:
Predictive: The study indicates that the mutation status of the K-ras gene significantly affects the response to cetuximab treatment, with wild-type K-ras tumors showing improved overall and progression-free survival compared to those with mutated K-ras tumors. This correlation between K-ras mutation status and treatment response classifies the evidence as predictive.
Prognostic: The abstract mentions that the mutation status of the K-ras gene has treatment-independent prognostic value, suggesting that it correlates with survival outcomes regardless of therapy. This aligns with the definition of prognostic evidence, as it indicates the potential impact of K-ras mutation status on overall survival and progression-free survival.
nan
Predictive evidence:
Predictive: The study discusses how BCR-ABL kinase domain point mutations lead to resistance against the ABL kinase inhibitor imatinib, indicating that these mutations correlate with treatment response and resistance to specific therapies. The mention of BMS-354825's effectiveness against imatinib-resistant mutants further supports the predictive nature of these variants in relation to therapy outcomes.
nan
Oncogenic evidence:
Oncogenic: The study identifies a novel double L858R + E884K somatic mutation of the EGFR, indicating that this variant contributes to tumor development or progression in the context of the patient's lung adenocarcinoma. The presence of this mutation is associated with the patient's disease state and treatment resistance, highlighting its role in oncogenesis.
nan
Predictive, Diagnostic evidence:
Predictive: The study discusses the T790M mutation as a secondary mutation that contributes to acquired resistance to gefitinib, indicating a correlation with treatment response. This aligns with the definition of predictive evidence, as it relates to how the presence of the T790M variant affects the efficacy of a specific therapy.
Diagnostic: The T790M mutation is mentioned in the context of identifying tumors with acquired resistance to gefitinib, suggesting its role in classifying or confirming a subtype of non-small cell lung cancer. This supports the diagnostic evidence type, as it is used to define a specific condition related to treatment resistance.
nan
Predictive, Oncogenic, Functional evidence:
Predictive: The abstract discusses a patient with an EGFR mutation who was initially responsive to gefitinib but later relapsed due to a second mutation (threonine-to-methionine) that resulted in gefitinib resistance, indicating a correlation between the variant and treatment response.
Oncogenic: The presence of the threonine-to-methionine mutation is described as contributing to gefitinib resistance, which suggests that this somatic variant plays a role in tumor progression and development in the context of non-small-cell lung cancer.
Functional: The abstract mentions that structural modeling and biochemical studies demonstrated that the threonine-to-methionine mutation alters the response to gefitinib, indicating a change in molecular function related to drug interaction.
nan
Predictive, Diagnostic evidence:
Predictive: The study discusses the use of erlotinib as maintenance therapy for patients with non-small-cell lung cancer (NSCLC) and reports that median progression-free survival (PFS) was significantly longer with erlotinib compared to placebo, indicating a correlation between the EGFR status and response to the therapy. This suggests that the variant related to EGFR may predict sensitivity to erlotinib treatment.
Diagnostic: The study stratified patients by EGFR immunohistochemistry status, indicating that the presence of EGFR protein overexpression is used to classify patients and assess their eligibility for erlotinib treatment. This demonstrates the role of the EGFR variant in defining a specific disease subtype within NSCLC.
nan
Predictive, Oncogenic evidence:
Predictive: The study discusses the response of a patient with a BRAF V600E mutation to vemurafenib, indicating that the presence of this variant correlates with a dramatic therapeutic response, thus providing evidence for its predictive value in treatment outcomes.
Oncogenic: The BRAF V600E mutation is mentioned in the context of contributing to the activity of the mitogen-activated protein kinase pathway in malignant peripheral nerve sheath tumors, suggesting its role in tumor development or progression.
nan
Predictive, Oncogenic evidence:
Predictive: The study discusses how the presence of the BRAF(V600E) variant correlates with the clinical activity of RAF inhibitors in melanoma patients, indicating that this variant is associated with treatment response and resistance mechanisms.
Oncogenic: The evidence presented shows that the BRAF(V600E) variant contributes to tumor development and progression, particularly through its role in dimerization and resistance to RAF inhibitors, which is characteristic of oncogenic behavior.
nan
nan evidence:
Missing abstract
nan
Predictive, Prognostic evidence:
Predictive: The study discusses the response rates to high-dose IL-2 therapy in patients with metastatic melanoma, indicating that baseline performance status and prior systemic therapy are predictive factors for response to treatment. This aligns with the predictive evidence type as it correlates the variant's presence with treatment response.
Prognostic: The results mention that 28% of responding patients remain progression-free, and disease did not progress in any patient responding for more than 30 months, indicating a correlation between the variant and disease outcome independent of therapy. This supports the classification as prognostic evidence.
nan
Predictive, Oncogenic evidence:
Predictive: The study discusses the response rate to the RAF-selective inhibitor PLX4032 in patients with B-RAF(V600E)-positive melanomas, indicating that the presence of this variant correlates with treatment response. The mention of an "80% anti-tumour response rate" highlights the predictive nature of the variant in relation to therapy effectiveness.
Oncogenic: The abstract states that B-RAF(V600E) mutations occur in a significant percentage of melanomas and are implicated in tumor development, which supports the classification of this variant as oncogenic. The evidence of acquired resistance mechanisms further emphasizes its role in tumor progression.
nan
Predictive, Prognostic, Oncogenic evidence:
Predictive: The study demonstrates that the BRAF V600E mutation correlates with improved response rates to the BRAF kinase inhibitor vemurafenib, indicating its predictive value for treatment efficacy in metastatic melanoma.
Prognostic: The results show that patients with the BRAF V600E mutation treated with vemurafenib had significantly improved overall survival rates compared to those treated with dacarbazine, suggesting that this variant is prognostic for better disease outcomes.
Oncogenic: The presence of the BRAF V600E mutation is implicated in the tumor development and progression in melanoma, as evidenced by the improved survival outcomes associated with targeted therapy.
nan
Predictive, Diagnostic, Prognostic, Oncogenic evidence:
Predictive: The study discusses how KRAS mutations correlate with resistance to cetuximab, indicating that these mutations are predictive of treatment response. Specifically, it highlights that KRAS mutants had a significantly lower response rate compared to wild types, demonstrating the variant's role in predicting therapy efficacy.
Diagnostic: The abstract mentions that tumors are profiled for KRAS mutations before treatment, indicating that the presence of these mutations is used to classify patients for therapy. This suggests that KRAS mutations serve as a diagnostic marker in determining treatment eligibility for cetuximab.
Prognostic: The findings indicate that KRAS mutations are associated with worse overall survival and progression-free survival, independent of therapy. The reported median overall survival and progression-free survival rates for KRAS mutants versus wild types provide evidence of the prognostic implications of these variants.
Oncogenic: The study implies that KRAS mutations contribute to tumor behavior, as they are associated with a lack of benefit from cetuximab treatment. This suggests that KRAS mutations play a role in tumor development or progression, aligning with the definition of oncogenic variants.
nan
Predictive, Prognostic evidence:
Predictive: The study identifies that patients with tumors lacking K-ras mutations have a significantly higher disease control rate with cetuximab treatment, indicating a correlation between the K-ras variant status and treatment response. Additionally, high expression levels of the EGFR ligands epiregulin and amphiregulin are associated with better clinical responses to cetuximab, further supporting the predictive nature of these markers for therapy outcomes.
Prognostic: The results indicate that patients with high expression of EREG or AREG have significantly longer progression-free survival compared to those with low expression, suggesting that these expression levels correlate with disease outcome independent of therapy.
nan
Oncogenic evidence:
Oncogenic: The abstract discusses BRAF mutations, including V599E, as contributing to tumor development in colorectal cancer, indicating that these mutations are biologically similar to RAS mutations and occur at a specific stage of neoplastic transformation. The presence of BRAF mutations in colorectal adenocarcinomas suggests their role in tumor progression, which aligns with the definition of oncogenic variants.
nan
Predictive, Prognostic evidence:
Prognostic: The study reports that patients with K-ras mutations had significantly poorer overall survival compared to those without K-ras mutations, indicating that the presence of K-ras mutations correlates with disease outcome independent of therapy. The multivariate analysis further supports this association with a hazard ratio of 2.9, confirming the prognostic significance of K-ras mutations in colorectal cancer.
Predictive: The abstract states that the presence of K-ras mutations predicts poor patient prognosis in colorectal cancer, suggesting a correlation with treatment response or resistance, which aligns with the predictive evidence type.
nan
Predictive evidence:
Predictive: The study discusses the association of mutations, including the V600E BRAF mutation, with tumor resistance to panitumumab, indicating that the presence of certain mutations may correlate with treatment response. The conclusion suggests that the absence of a K-ras mutation is associated with a better response to panitumumab, which implies a predictive role for these mutations in treatment outcomes.
nan
Predisposing, Functional evidence:
Predisposing: The abstract mentions "germline mutations that affect components of the Ras-Raf-MEK-ERK pathway," indicating that these inherited mutations confer risk for developmental disorders, which aligns with the definition of predisposing variants.
Functional: The abstract states that "many of these mutant alleles encode proteins with aberrant biochemical and functional properties," suggesting that the variants alter molecular or biochemical function, which supports the functional evidence type.
nan
Predictive, Diagnostic evidence:
Predictive: The study indicates that CRBN depletion leads to resistance to lenalidomide and pomalidomide, suggesting that the variant correlates with treatment response, specifically highlighting the role of CRBN in the efficacy of these therapies.
Diagnostic: The mention of CRBN as a possible biomarker for the clinical assessment of antimyeloma efficacy implies that it is used to classify or define the response to treatment in patients, thus supporting its role in diagnostic contexts.
nan
Predictive, Oncogenic evidence:
Predictive: The study discusses how secondary kinase mutations in KIT or PDGFRA are associated with decreased imatinib sensitivity, indicating a correlation between these mutations and resistance to therapy. This suggests that the presence of these mutations can predict the response to imatinib treatment in patients with advanced GISTs.
Oncogenic: The abstract mentions that gastrointestinal stromal tumors (GISTs) commonly harbor oncogenic mutations of the KIT or PDGFRA kinases, which contribute to tumor development and progression. This indicates that these mutations play a role in the oncogenic process within GISTs.
nan
Oncogenic, Functional evidence:
Oncogenic: The study demonstrates that KMT2D functions as a tumor suppressor and that its genetic ablation in B cells promotes lymphoma development in mice, indicating that mutations in KMT2D contribute to tumor progression.
Functional: The research shows that KMT2D affects the methylation of lysine 4 on histone H3 (H3K4) and alters the expression of a set of genes involved in critical signaling pathways, suggesting that the variant alters molecular function related to gene regulation.
nan
nan evidence:
Missing abstract
nan
nan evidence:
Missing abstract
nan
nan evidence:
Missing abstract
nan
nan evidence:
Missing abstract
nan
Predictive evidence:
Predictive: The study indicates that IDH1 and IDH2 mutations may predict a favorable response to DNA methyltransferase inhibitors (DNMTIs) in patients with AML, as evidenced by the higher remission rates in patients with these mutations compared to those without. The odds ratio of achieving a response after treatment further supports the predictive nature of these mutations in relation to therapy outcomes.
nan
Predictive evidence:
Predictive: The study indicates that mutated TET2 status independently predicted a higher response rate to azacitidine (AZA) treatment, with a response rate of 82% in patients with TET2 mutations compared to 45% in wild-type patients (P=0.007). This suggests that the presence of TET2 mutations correlates with sensitivity to the therapy, fulfilling the criteria for predictive evidence.
nan
Functional evidence:
Functional: The variant R111A is referenced in the context of immunohistochemical staining with the antibody clone EPNCIR111A, indicating that it is being studied for its impact on protein expression or function. This suggests that the variant may alter the molecular or biochemical function of the protein involved.
nan
Oncogenic evidence:
Oncogenic: The abstract discusses the identification of inactivating mutations in the SMARCA4 gene, which is implicated in the development of small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). The presence of the p.Pro1180fs variant in the SCCOHT-1 tumor cell line suggests that it contributes to tumor development or progression, aligning with the definition of an oncogenic variant.
nan
Predisposing, Oncogenic evidence:
Predisposing: The study identifies deleterious germline mutations in SMARCA4 that segregate within families affected by small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), indicating that these mutations confer inherited risk for developing this malignancy.
Oncogenic: The presence of somatic mutations or loss of the wild-type allele of SMARCA4 in familial tumors suggests that these alterations contribute to tumor development or progression in SCCOHT.
nan
Predisposing evidence:
Predisposing: The study discusses germline mutations and deletions of SMARCB1/INI1 that predispose patients to rhabdoid tumors and schwannomatosis, indicating that these variants confer inherited risk for developing these diseases. The mention of parent-to-child transmission of mutated copies of SMARCB1 further supports the classification as predisposing.
nan
Diagnostic, Oncogenic evidence:
Oncogenic: The study identifies a rare activating mutation of AKT1 (E17K) in melanoma, suggesting that this somatic variant contributes to tumor development or progression, as it is associated with activation of the AKT pathway in human melanoma cells.
Diagnostic: The presence of the AKT1 E17K mutation is discussed in the context of its identification in melanoma specimens, indicating its potential role in classifying or defining a subtype of melanoma with specific genetic alterations.
nan
Predictive, Oncogenic evidence:
Oncogenic: The study demonstrates that mutations at the PH-KD interface of AKT1 lead to constitutive activation of the protein, contributing to oncogenic signaling, which indicates that these somatic mutations play a role in tumor development or progression.
Predictive: The findings suggest that the AKT1 somatic mutants are not effectively inhibited by allosteric AKT inhibitors, indicating a potential resistance to therapy, which correlates with the variant's impact on treatment response.
nan
Predictive, Oncogenic evidence:
Oncogenic: The study demonstrates that mutations at the PH-KD interface of AKT1 lead to constitutive activation of the protein, contributing to oncogenic signaling, which indicates that these somatic variants play a role in tumor development or progression.
Predictive: The findings suggest that the AKT1 somatic mutants are not effectively inhibited by allosteric AKT inhibitors, indicating a potential resistance to therapy, which correlates with the variant's impact on treatment response.
nan
Predictive, Oncogenic evidence:
Oncogenic: The study demonstrates that mutations at the PH-KD interface of AKT1 lead to constitutive activation of the protein, contributing to oncogenic signaling, which indicates that these somatic variants play a role in tumor development or progression.
Predictive: The findings suggest that the AKT1 somatic mutants are not effectively inhibited by allosteric AKT inhibitors, indicating a potential resistance to therapy, which correlates with the variant's impact on treatment response.
nan
Prognostic, Oncogenic evidence:
Oncogenic: The study identifies somatic mutations in gallbladder carcinoma (GBC) and highlights the role of the ErbB signaling pathway in GBC pathogenesis, indicating that these mutations contribute to tumor development or progression.
Prognostic: The multivariate analyses show that cases with ErbB pathway mutations have a worse outcome, suggesting a correlation between these mutations and disease prognosis independent of therapy.
nan
Oncogenic evidence:
Oncogenic: The study reports the identification of ERBB3 somatic mutations that transformed colonic and breast epithelial cells in a ligand-independent manner, indicating that these mutations contribute to tumor development. Additionally, the mutant ERBB3's oncogenic activity was shown to be dependent on kinase-active ERBB2, further supporting its role in cancer progression.
nan
Diagnostic, Oncogenic, Functional evidence:
Diagnostic: The study presents evidence that a germline mutation involving codon 600 of BRAF is associated with the development of cardio-facio-cutaneous (CFC) syndrome, indicating its role in defining a specific disease phenotype.
Oncogenic: The abstract discusses the somatic mutation p.V600E as frequently found in various tumor types, suggesting that mutations at codon 600, including p.V600G, contribute to tumor development or progression.
Functional: The in vitro analysis demonstrates that the p.V600G mutation alters the molecular function of BRAF by leading to increased ERK and ELK phosphorylation compared to wild-type BRAF, indicating a change in biochemical activity.
nan
Oncogenic, Functional evidence:
Oncogenic: The study demonstrates that NRAS mutation leads to increased cellular proliferation and is potently tumorigenic, indicating that this somatic variant contributes to tumor development in melanoma. The comparison of transformation efficiencies between NRAS and KRAS further supports the oncogenic role of NRAS in this context.
Functional: The findings indicate that NRAS mutation enhances MYC activity in melanocytes, suggesting that this variant alters molecular function, specifically in the context of signaling pathways. This alteration in activity is critical for understanding the mechanisms behind NRAS's role in melanoma.
nan
Predictive, Oncogenic, Functional evidence:
Functional: The study functionally characterized the G309A mutation using in vitro kinase assays, indicating that it alters molecular function related to HER2 activity. This suggests that the variant has a specific biochemical impact that contributes to its role in tumorigenesis.
Oncogenic: The abstract states that the majority of HER2 somatic mutations, including G309A, are activating mutations that likely drive tumorigenesis in breast cancer. This indicates that the variant contributes to tumor development or progression.
Predictive: The findings suggest that patients with HER2 mutation-positive breast cancers, including those with the G309A mutation, could benefit from HER2-targeted therapies like neratinib, indicating a correlation with treatment response.
nan
Predictive, Oncogenic evidence:
Oncogenic: The study discusses somatic mutations in JAK3 that contribute to the development of Adult T-cell leukemia/lymphoma (ATLL), indicating that these mutations play a role in tumor progression. The mention of "gain of function" in JAK3 further supports its contribution to oncogenesis in this context.
Predictive: The abstract notes that the mutant JAK3s are inhibited with a specific kinase inhibitor that is already in human clinical testing, suggesting a correlation between the presence of these mutations and the response to targeted therapy. This indicates that the variant may influence treatment outcomes in patients with ATLL.
nan
Oncogenic evidence:
Oncogenic: The M511I mutation in JAK3 has been shown to contribute to tumor development, as it induced T-ALL in mice when over-expressed in IL3 dependent 32D cells. This evidence supports the classification of M511I as an oncogenic variant due to its role in promoting leukemia.
nan
Predictive, Oncogenic evidence:
Oncogenic: The study identifies the JAK3 variant V674A as an activating allele that can transform a lymphoid pro-B-cell line to IL-3-independent growth, indicating its role in tumor development or progression. This transformation capability supports the classification of V674A as an oncogenic variant.
Predictive: The results demonstrate that treatment with the compound NSC114792 leads to a decrease in the viability of BaF3-JAK3V674A cells in a dose-dependent manner, suggesting that the presence of the V674A variant predicts sensitivity to this specific therapy targeting JAK3 activity.
nan
Predictive, Prognostic evidence:
Predictive: The presence of NOTCH1 mutations was significantly correlated with a good prednisone response and favorable minimal residual disease (MRD) kinetics, indicating that these mutations predict a more rapid early treatment response in children with T-ALL.
Prognostic: Activating NOTCH1 mutations specified a large subgroup of patients with an excellent prognosis, suggesting that these mutations correlate with favorable long-term outcomes independent of therapy.
nan
Predictive, Prognostic, Functional evidence:
Predictive: The abstract states that KRAS mutations are confirmed as predictive biomarkers of response to epidermal growth factor receptor (EGFR)-targeted therapies, indicating a correlation between these mutations and treatment outcomes.
Prognostic: The abstract mentions that mutations in exon 4 of KRAS predict a more favorable clinical outcome in patients with colorectal cancer, suggesting that these mutations are associated with disease outcomes independent of therapy.
Functional: The abstract describes that exon 4 KRAS mutations were associated with lower levels of GTP-bound RAS in isogenic models, indicating that these mutations alter the molecular function of the RAS protein.
nan
Oncogenic evidence:
Oncogenic: The study discusses a novel point mutation in the K-ras gene that contributes to tumor development, as evidenced by the transformation assays in NIH3T3 cells, indicating that the K-ras Lys22 mutation plays a role in tumor cell growth in vivo. The mention of transformed morphology and tumorigenicity supports the classification of this variant as oncogenic.
nan
Predictive, Oncogenic evidence:
Oncogenic: The study demonstrates that novel recurring extracellular domain mutations of the ERBB2 gene are potently oncogenic, as evidenced by their ability to activate transformation assays and promote cellular processes such as motility through tyrosine phosphorylation.
Predictive: The results suggest that patients harboring ERBB2 mutations could benefit from ERBB2-directed therapy, indicating a correlation between these mutations and response to specific treatment with small-molecule inhibitors.
nan
Predictive, Functional evidence:
Functional: The abstract discusses how the HER2(YVMA) mutant transphosphorylates kinase-dead EGFR(K721R) and EGFR(WT), indicating that the K721R variant alters the molecular function of the EGFR protein in the presence of HER2 mutations and tyrosine kinase inhibitors. This suggests a change in biochemical activity related to the variant.
Predictive: The study mentions that cancer cells expressing the HER2(YVMA) mutation remain sensitive to HER2-targeted therapies but are insensitive to EGFR TKIs, indicating that the K721R variant's presence correlates with treatment response, specifically in the context of therapy with HER2 inhibitors.
nan
Predictive, Prognostic evidence:
Prognostic: The study indicates that DNMT3A mutations, particularly those at the R882 position, are associated with a poor outcome in acute myeloid leukemia (AML) patients, suggesting a correlation with disease progression and overall survival.
Predictive: The findings suggest that DNMT3A mutations, including those at the R882 position, could serve as predictive factors for response to idarubicin treatment, indicating their potential role in guiding therapy decisions for AML patients.
nan
Predictive, Functional evidence:
Predictive: The study discusses the imatinib sensitivity associated with the CSF1R-Y571D mutation, indicating that this variant correlates with a response to therapy, specifically imatinib treatment.
Functional: The Y571D variant is shown to result in increased colony growth and constitutive phosphorylation of CSF1R, demonstrating that it alters the molecular function of the receptor, which is supported by the experimental findings in the cell line GDM1.
nan
Diagnostic, Oncogenic evidence:
Diagnostic: The study discusses the KRAS mutation analysis as a predictive biomarker in colorectal cancer, indicating that the presence of specific mutations, including glycine to aspartate, is essential for defining the mutational status of tumors prior to treatment. This establishes the variant's role in classifying and confirming the disease subtype.
Oncogenic: The presence of the glycine to aspartate mutation in codon 12 is highlighted as a frequent mutation in colorectal cancer, suggesting its contribution to tumor development and progression, which aligns with the definition of oncogenic variants.
nan
Oncogenic evidence:
Oncogenic: The study discusses ras-gene mutations occurring in a significant percentage of adenomas and carcinomas, indicating that these mutations contribute to tumor development and progression in colorectal cancer. The accumulation of these molecular alterations aligns with the clinical progression of tumors, supporting the role of these mutations in oncogenesis.
nan
Oncogenic evidence:
Oncogenic: The abstract discusses the role of Notch in neoplasias, indicating that Notch can act as an oncogene or tumor suppressor, which suggests that variants in the Notch signaling pathway may contribute to tumor development or progression. This aligns with the definition of oncogenic evidence, as it implies a direct involvement in cancer biology.
nan
Functional evidence:
Functional: The abstract states that "functional analysis showed no alteration compared to non-mutated BCR-ABL," indicating that the K247R variant does not change the molecular or biochemical function of the BCR-ABL protein. This suggests that the variant's presence does not affect the protein's activity or behavior in a significant way.
nan
Predictive, Diagnostic evidence:
Predictive: The study indicates that the presence of the T315I mutation is predictive of relapse despite a molecular response to imatinib, suggesting that monitoring this variant can inform therapeutic management decisions.
Diagnostic: The analysis of T315I mutated BCR-ABL clones throughout the CML history of patients suggests that this variant can be used to classify and monitor the disease progression in chronic myeloid leukemia (CML).
nan
Predictive, Functional evidence:
Predictive: The study discusses the Thr315Ile mutation in the context of resistance to the tyrosine kinase inhibitor STI571 in chronic myeloid leukemia (CML), indicating that this variant correlates with treatment resistance, which is a key aspect of predictive evidence.
Functional: The presence of the Thr315Ile mutation is associated with clonal selection due to the functional inhibiting effect of STI571, suggesting that this variant alters the molecular response to the therapy, which aligns with functional evidence.
nan
nan evidence:
Missing abstract
nan
Predictive, Diagnostic, Oncogenic evidence:
Diagnostic: The study identifies the Glu255Lys mutation in patients with Ph+ acute lymphoblastic leukemia (ALL), suggesting its role in classifying or confirming the disease prior to treatment with STI571.
Predictive: The presence of the Glu255Lys mutation is associated with the development of resistance to STI571 treatment, indicating that it may predict treatment response or resistance in patients with Ph+ ALL.
Oncogenic: The Glu255Lys mutation is described as an oncogenic variant that contributes to the development of resistance in leukemic cells, highlighting its role in tumor progression.
nan
Predictive evidence:
Predictive: The abstract discusses how the T315I variant is resistant to the therapies dasatinib and nilotinib, indicating that it correlates with resistance to these specific treatments. The mention of T315I being the only mutant isolated at drug concentrations equivalent to maximal achievable plasma trough levels further emphasizes its role in treatment resistance.
nan
nan evidence:
Missing abstract
nan
Predictive, Diagnostic evidence:
Predictive: The abstract discusses the importance of the BCR-ABL mutation profile in determining the response to second-generation tyrosine kinase inhibitors (TKIs) like dasatinib and nilotinib, indicating that certain mutations correlate with treatment efficacy. This suggests that the variant's presence can influence the choice of therapy and its expected success, which aligns with predictive evidence.
Diagnostic: The mention of the BCR-ABL mutation profile as a factor in treatment decisions implies that these mutations are used to classify or define the patient's disease state, particularly in the context of chronic myeloid leukemia and resistance to imatinib therapy. This supports the classification of the variant as diagnostic.
nan
Predictive evidence:
Predictive: The study identifies EGFR mutations as the strongest predictive biomarker for progression-free survival (PFS) and tumor response to gefitinib compared to carboplatin/paclitaxel, indicating a correlation between the presence of these mutations and treatment efficacy. The results highlight that the predictive value of EGFR gene copy number is influenced by the presence of coexisting EGFR mutations, further supporting the predictive nature of these biomarkers in treatment response.
nan
Diagnostic, Functional evidence:
Diagnostic: The study discusses the c.38G>A KRAS mutation in the context of mutation detection methods, indicating its role in distinguishing true mutations from artefacts, which suggests its use in defining or confirming a disease or subtype.
Functional: The mention of the c.38G>A variant in the context of mutation detection implies that it may alter the molecular function of the KRAS protein, as the study focuses on the sensitivity of detecting this specific mutation through various methods.
nan
Predictive, Diagnostic evidence:
Diagnostic: The abstract states that "neither mutation of EGFR nor increased copy number of EGFR or HER2 was diagnostic of response to gefitinib," indicating that the presence of the L858R variant does not serve as a reliable biomarker for treatment response, which aligns with the definition of diagnostic evidence.
Predictive: The abstract mentions the need for "additional predictive biomarkers beyond EGFR status," suggesting that while the L858R variant is not predictive of response to gefitinib, it is still discussed in the context of treatment outcomes, which fits the predictive evidence type.
nan
Predictive, Oncogenic evidence:
Predictive: The study discusses how mutant EGFRs in NSCLCs correlate with resistance to conventional chemotherapeutic drugs and sensitivity to gefitinib, indicating that these variants influence treatment response. The mention of "inhibition of those signals by gefitinib may contribute to the drug's efficacy" further supports this classification.
Oncogenic: The abstract describes how mutant EGFRs promote cell survival and are involved in signaling pathways that contribute to tumor development, indicating their role in oncogenesis. The activation of specific signaling pathways by these mutations suggests they contribute to tumor progression in NSCLC.
nan
Predictive, Functional evidence:
Predictive: The study identifies specific mutations in the EGFR gene that correlate with clinical responsiveness to the tyrosine kinase inhibitor gefitinib, indicating that these mutations are associated with sensitivity to this therapy. The results show that patients with these mutations had a rapid and dramatic clinical response to gefitinib, supporting the predictive nature of the variant in treatment outcomes.
Functional: The identified EGFR mutations demonstrated enhanced tyrosine kinase activity in response to epidermal growth factor and increased sensitivity to gefitinib in vitro, indicating that these mutations alter the molecular function of the EGFR protein. This functional alteration is critical for understanding how these mutations contribute to the observed therapeutic responses.
nan
Predictive, Oncogenic evidence:
Predictive: The abstract states that "classical mutations in the EGFR tyrosine kinase domain... have been associated with sensitivity to tyrosine kinase inhibitors (TKIs) in patients with NSCLC," indicating that the L858R mutation correlates with response to therapy. Additionally, the results section mentions that "somatic mutations in the tyrosine kinase domain of the EGFR gene... were significantly correlated with clinical response to gefitinib therapy," further supporting the predictive nature of this variant in relation to treatment outcomes.
Oncogenic: The abstract discusses "classical mutations" in the EGFR gene, including L858R, which are known to contribute to tumor development in non-small cell lung cancer (NSCLC). This classification is supported by the context of the study focusing on mutations that drive cancer progression and their association with treatment response.
nan
Predictive evidence:
Predictive: The presence of a mutation in the epidermal growth factor receptor gene (EGFR) is described as a strong predictor of a better outcome with gefitinib, indicating that the variant correlates with response to this specific therapy. The results show that patients with the EGFR mutation had significantly longer progression-free survival when treated with gefitinib compared to those treated with carboplatin-paclitaxel.
nan
Oncogenic evidence:
Oncogenic: The study identifies the L861Q mutation in the EGFR kinase domain as a rare event in glioblastomas, indicating its potential role in tumor development or progression, particularly as it is located in a region associated with mutations in lung cancer. This suggests that the variant may contribute to oncogenic processes in this context.
nan
Predictive, Oncogenic evidence:
Predictive: The abstract discusses how the B-RAFV600E mutation predicts a dependency on the MAPK signaling cascade in melanoma, which is further supported by the success of RAF and MEK inhibitors in clinical trials. This indicates a correlation between the variant and response to specific therapies.
Oncogenic: The abstract mentions that oncogenic mutations in B-RAF, including B-RAFV600E, are found in a significant percentage of malignant melanomas, suggesting that this variant contributes to tumor development or progression. Additionally, the results section describes the use of B-RAFV600E cell lines to study resistance mechanisms, further supporting its role in oncogenesis.
nan
Oncogenic evidence:
Oncogenic: The study demonstrates that gain-of-function BRAF signaling is strongly associated with in vivo tumorigenicity, indicating that the BRAF variant contributes to tumor development and progression. This is supported by the evidence of tumor regression upon BRAF suppression in xenograft models, which highlights its role in promoting tumor cell proliferation and survival.
nan
Predictive, Oncogenic evidence:
Predictive: The study discusses the response of patients with the V600E BRAF mutation to the drug PLX4032, indicating that treatment led to partial or complete tumor regression in a significant number of patients. This suggests a correlation between the presence of the V600E mutation and the effectiveness of the therapy, which is a key aspect of predictive evidence.
Oncogenic: The V600E mutation in BRAF is identified as a somatic mutation that contributes to tumor development in melanoma, as the study focuses on patients with this specific mutation and its role in the context of targeted therapy. This aligns with the definition of oncogenic evidence, as the mutation is implicated in the progression of the disease.
nan
Oncogenic evidence:
Oncogenic: The study discusses various B-RAF mutations, indicating that they contribute to tumor development by showing elevated kinase activity and signaling to ERK, which is a hallmark of oncogenic behavior. The mention of the activation of C-RAF and the role of these mutations in converting B-RAF into an active conformation further supports their oncogenic potential.
nan
Predictive evidence:
Predictive: The study discusses the effects of the multikinase inhibitor INNO-406 on cells harboring the KIT mutant V560G, indicating that the presence of this variant may influence the response to therapy, as evidenced by the differential inhibition of proliferation in HMC-1.1 cells compared to HMC-1.2 cells. This suggests a correlation between the V560G variant and sensitivity to the drug, which aligns with the predictive evidence type.
nan
Predictive, Diagnostic, Oncogenic evidence:
Predictive: The D816V substitution in the activation loop of KIT results in relative resistance to the kinase inhibitor imatinib (Gleevec), indicating that this variant correlates with treatment response.
Diagnostic: The D816V mutation occurs in 80 to 95% of adult systemic mastocytosis (SM) cases, highlighting its significance in the detection and diagnosis of this disease.
Oncogenic: The abstract discusses oncogenic mutations of the receptor tyrosine kinase KIT, including D816V and D816F, which contribute to the pathogenesis of gastrointestinal stromal tumors and systemic mastocytosis, indicating their role in tumor development.
nan
Oncogenic evidence:
Oncogenic: The study reports that somatic c-KIT mutations, specifically the substitution of valine for aspartate at codon 816, are characteristic of sporadic adult mastocytosis and contribute to the spontaneous activation of the mast cell growth factor receptor, indicating a role in tumor development or progression.
nan
Predictive, Oncogenic evidence:
Oncogenic: The study indicates that activating mutations in KIT, including D816V, may contribute to tumorigenesis in a subset of seminomas, suggesting a role in tumor development or progression. This is supported by the observation of constitutive phosphorylation of the mutant isoforms, indicating their involvement in oncogenic signaling pathways.
Predictive: The abstract mentions that D816V and D816H were resistant to imatinib mesylate, which implies a correlation with resistance to this specific therapy. This suggests that the presence of these mutations can predict the response to treatment with imatinib.
nan
Predictive, Prognostic evidence:
Predictive: The study examines the correlation between mutations in KIT and PDGFRA and clinical response to imatinib, indicating that the mutational status of these oncoproteins is predictive of clinical response to the therapy. Specifically, it reports that patients with exon 11 KIT mutations had a significantly higher partial response rate to imatinib compared to those with exon 9 mutations or no detectable mutations.
Prognostic: The results indicate that patients with tumors containing exon 11 KIT mutations had a longer event-free and overall survival compared to those with exon 9 mutations or no detectable mutations, suggesting that this variant correlates with better disease outcomes independent of therapy.
nan
Predictive, Oncogenic evidence:
Predictive: The abstract discusses how secondary mutations in the target kinase contribute to acquired resistance to tyrosine kinase inhibitors, indicating a correlation between these mutations and treatment response. This suggests that the variant may influence sensitivity or resistance to specific therapies.
Oncogenic: The mention of KIT and PDGFRA mutations being involved in the pathogenesis of gastrointestinal stromal tumors indicates that these somatic variants contribute to tumor development or progression. This aligns with the definition of oncogenic variants as they are implicated in cancer biology.
nan
Oncogenic evidence:
Oncogenic: The study identifies oncogenic mutations in the KIT gene in a significant proportion of melanoma tumors, indicating that these mutations contribute to tumor development in specific melanoma subtypes. The presence of KIT mutations and their association with increased protein levels further supports the role of KIT as an important oncogene in melanoma.
nan
Oncogenic evidence:
Oncogenic: The study discusses gain-of-function mutations in the c-kit gene, specifically noting that the mutant KIT exhibited constitutive phosphorylation and strong kinase activity, which are indicative of its role in tumor development and progression. The ability of the transfectant to grow autonomously and form tumors in nude mice further supports the oncogenic nature of the variant.
nan
Predictive, Prognostic evidence:
Predictive: The study demonstrates that the V560G variant of Kit shows increased sensitivity to Imatinib, with a lower GI50 compared to wild-type Kit, indicating a correlation with treatment response. This suggests that the presence of the V560G mutation may predict a better response to Imatinib therapy in gastrointestinal stromal tumors.
Prognostic: The abstract mentions that mutations in the juxtamembrane region of Kit, including V560G, have been linked to poor prognosis in gastrointestinal stromal tumors, indicating that this variant may correlate with disease outcome independent of therapy.
nan
Oncogenic evidence:
Oncogenic: The study discusses mutations in the c-kit proto-oncogene, specifically the substitutions of Gly-560 for Val and Val-816 for Asp, which are implicated in the constitutive activation of the c-kit receptor. This activation is associated with tumor development in the context of mast cell leukemia, indicating that these mutations contribute to oncogenic processes.
nan
Oncogenic evidence:
Oncogenic: The study demonstrates that the Val-559-->Gly (G559) mutation in the c-kit receptor tyrosine kinase leads to constitutive activation and factor-independent growth in murine pro-B-type cells, indicating that this somatic variant contributes to tumor development and progression. Additionally, the injection of cells expressing KITG559 into nude mice resulted in tumor formation and rapid onset of leukemia, further supporting its oncogenic role.
nan
Functional evidence:
Functional: The study demonstrates that the valine to alanine substitution at residue 536 (V536A) in the PDGFbetaR leads to increased tyrosine kinase activity and allows cells to survive and proliferate without growth factors, indicating that this variant alters the molecular function of the receptor. The findings suggest that the mutation enhances the receptor's activity, which is a clear alteration in biochemical function.
nan
Predictive evidence:
Predictive: The study indicates that the Val559Ile mutation in the c-kit gene is associated with resistance to imatinib therapy, as it was found that imatinib inhibited autophosphorylation of the mutant KIT with Val559Asp but not with Val559Ile. This suggests that the presence of the Val559Ile variant correlates with a lack of response to this specific treatment.
nan
Predictive, Oncogenic evidence:
Predictive: The study assesses the clinical effects of imatinib mesylate in patients with melanoma harboring KIT alterations, indicating a correlation between the presence of these mutations and the response to therapy. The results show that response rates were better in cases with specific mutations, suggesting that these alterations predict sensitivity to treatment with imatinib.
Oncogenic: The abstract discusses activating mutations and amplification of the KIT gene in melanoma, which are implicated in tumor development and progression. The focus on the effects of KIT inhibition further supports the notion that these alterations contribute to the oncogenic process in this subset of melanoma.
nan
Predisposing, Oncogenic evidence:
Oncogenic: The substitution of Glu for Lys(642) is described as an oncogenic mutation in the tyrosine kinase domain of KIT, indicating that it contributes to tumor development or progression, as demonstrated by the proliferation assay and tumor formation in nude mice.
Predisposing: The variant is noted as a germline heterozygous mutation that causes diffuse hyperplasia of myenteric interstitial cells of Cajal during embryonic development and leads to the occurrence of multiple gastrointestinal stromal tumors in adulthood, indicating an inherited risk for developing disease.
nan
Predictive, Oncogenic evidence:
Oncogenic: The study identifies KRAS mutations (G12A and G12V) in thymic tumors, indicating that these somatic variants contribute to tumor development or progression, as they are associated with specific tumor types (thymoma and thymic carcinoma).
Predictive: The results mention that the V560del KIT mutant was associated with similar sensitivities to imatinib and sunitinib, suggesting a correlation between the presence of specific mutations and the response to these therapies, which aligns with predictive evidence.
nan
Oncogenic evidence:
Oncogenic: The study demonstrates that mutations in the c-kit gene lead to the constitutive activation of the KIT protein, which is implicated in the malignant transformation of cells, indicating that these mutations contribute to tumor development. The stable transfection of mutant c-kit DNAs into Ba/F3 cells further supports the oncogenic role of these variants in gastrointestinal stromal tumors (GISTs).
nan
Predictive, Prognostic evidence:
Predictive: The study evaluates the impact of primary and secondary kinase genotype on sunitinib activity, indicating that specific mutations in the KIT gene correlate with clinical benefit and progression-free survival in patients treated with sunitinib after imatinib failure. This suggests that the variant's presence influences the response to therapy, classifying it as predictive evidence.
Prognostic: The results indicate that patients with specific KIT mutations (exon 9 and wild-type) have significantly longer progression-free survival and overall survival compared to those with other mutations, demonstrating that these variants correlate with disease outcomes independent of therapy. This supports the classification as prognostic evidence.
nan
Predictive evidence:
Predictive: The abstract discusses the impact of targeting KIT with tyrosine kinase inhibitors like imatinib and sunitinib in the treatment of gastrointestinal stromal tumors (GISTs), indicating a correlation between the KIT variant and response to these therapies. This suggests that the presence of the KIT variant may influence treatment outcomes, classifying it as predictive evidence.
nan
Predictive, Oncogenic evidence:
Predictive: The study discusses the correlation between KIT mutations and resistance to imatinib therapy in GIST patients, indicating that these mutations are associated with treatment response and resistance. The mention of "imatinib-acquired-resistance" and the investigation of downstream signaling profiles in relation to therapy highlights the predictive nature of the variant's impact on treatment outcomes.
Oncogenic: The presence of activating mutations in the KIT gene, particularly in the context of gastrointestinal stromal tumors, suggests that these mutations contribute to tumor development and progression. The identification of secondary KIT mutations in patients who developed resistance to imatinib further supports the oncogenic role of these variants in GISTs.
nan
Predictive evidence:
Predictive: The study demonstrates that the presence of the KIT exon 11-mutant genotype correlates with improved treatment outcomes in patients treated with imatinib, indicating a relationship between the genotype and response to therapy. This is evidenced by the significantly higher objective response rates and longer time to tumor progression for patients with the exon 11 mutation compared to those with exon 9 mutations and wild-type genotypes.
nan
Predictive, Oncogenic evidence:
Oncogenic: The abstract states that approximately 85% of GISTs have oncogenic mutations in KIT, which are responsible for constitutive kinase activation leading to cellular proliferation and survival. This indicates that the variant contributes to tumor development or progression.
Predictive: The abstract mentions that the progression-free and overall survival of patients with advanced disease is greatly improved by treatment with kinase inhibitors, indicating a correlation between the variant and response to therapy.
nan
Predictive evidence:
Predictive: The study discusses the response rates of patients with various types of CML and gastrointestinal stromal tumors to imatinib treatment, indicating that the BCR-ABL variant correlates with therapeutic response, as evidenced by the reported haematological and cytogenetic responses in patients treated with imatinib.
nan
Predictive, Oncogenic evidence:
Predictive: The study discusses the role of KIT mutations in response to the tyrosine kinase inhibitor imatinib, indicating that these mutations are associated with secondary resistance to therapy. This suggests a correlation between the presence of these mutations and treatment outcomes, which aligns with the predictive evidence type.
Oncogenic: The identification of newly acquired KIT mutations in GISTs suggests that these somatic mutations contribute to tumor progression and resistance to therapy, indicating their role in oncogenesis. The study highlights the presence of these mutations in tumor samples, supporting their classification as oncogenic variants.
nan
Predictive, Oncogenic evidence:
Oncogenic: The study identifies c-kit mutations, including Pro551Leu, as potential gain-of-function mutations that may be involved in the pathogenesis of adenoid cystic carcinoma of the salivary glands, indicating a role in tumor development.
Predictive: The abstract suggests a potential correlation between c-kit mutations, such as Pro551Leu, and the treatment of adenoid cystic carcinoma with tyrosine kinase inhibitors, indicating that this variant may influence treatment response.
nan
Diagnostic, Oncogenic evidence:
Diagnostic: The study discusses the identification of mutations, including p.R822H, in the context of performing mutational analysis in gastrointestinal stromal tumors, indicating its role in defining or confirming the presence of a disease.
Oncogenic: The presence of the p.R822H variant in the context of PDGFRA mutations suggests its potential contribution to tumor development or progression, as it is part of the mutational analysis performed on gastrointestinal stromal tumors.
nan
Oncogenic, Functional evidence:
Functional: The V536E mutation is described as stimulating Ba/F3 cell growth and signaling via ERK and STAT5 in the absence of ligand, indicating that it alters molecular function. This suggests that the mutation has a specific impact on the receptor's activity and signaling pathways.
Oncogenic: The V536E mutation is characterized as a gain-of-function mutant, which implies that it contributes to tumor development or progression, particularly in the context of glioblastoma. This classification is supported by the evidence that the mutation enhances cell growth and signaling, which are key features of oncogenic variants.
nan
Predictive, Prognostic evidence:
Predictive: The study indicates that none of the patients with the D842V substitution had a response to imatinib, suggesting that this variant correlates with resistance to the therapy. Additionally, the median progression-free survival for patients with D842V was significantly lower compared to those with other PDGFRA mutations, further supporting its predictive nature regarding treatment outcomes.
Prognostic: The median overall survival for patients with D842V substitutions was reported as 14.7 months, which provides evidence that this variant correlates with disease outcome independent of therapy. This suggests that the D842V variant may have a prognostic impact on survival in patients with advanced PDGFRA-mutant GISTs.
nan
Oncogenic evidence:
Oncogenic: The study discusses that activating mutations in the KIT receptor tyrosine kinase and intragenic activation mutations in PDGFRA serve as alternative and mutually exclusive oncogenic mechanisms in gastrointestinal stromal tumors (GISTs). This indicates that these mutations contribute to tumor development or progression.
nan
Oncogenic evidence:
Oncogenic: The abstract indicates that BRAF mutations (V600E) were found in gastrointestinal stromal tumors (GISTs) and suggests that these mutations have pathogenetic significance in wild type GISTs, implying that the variant contributes to tumor development or progression.
nan
Predictive, Oncogenic evidence:
Oncogenic: The study discusses how the R481G mutation, along with other PDGFRA mutations, contributes to tumor development as evidenced by the induction of leukemia-like disease in mice when these mutations were introduced into 32D cells. This indicates that the variant plays a role in the pathogenesis of hypereosinophilic syndrome (HES).
Predictive: The abstract mentions that oral imatinib treatment significantly decreased leukemic growth and prolonged survival in mice with PDGFRA mutations, suggesting that the R481G variant is associated with sensitivity to imatinib therapy. This indicates a predictive relationship between the variant and treatment response.
nan
Predictive, Oncogenic evidence:
Oncogenic: The study identifies the Val-561 to Asp mutation in PDGFR alpha as a constitutively activated mutation that induces autonomous proliferation of Ba/F3 cells, indicating its role in tumor development in GISTs without KIT mutations.
Predictive: The results show that the constitutive activation of PDGFR alpha with Val-561 to Asp was effectively inhibited by Imatinib mesylate, suggesting that this variant correlates with sensitivity to this specific therapy.
nan
Oncogenic, Functional evidence:
Oncogenic: The study discusses the H1047R variant as an activating cancer-linked somatic mutation that displays transforming activities in cell culture and has been shown to initiate tumorigenesis in transgenic mouse models, indicating its role in tumor development and progression.
Functional: The abstract mentions that both the H1047R and H1047L mutants show increased basal kinase activities and lipid binding, which suggests that these variants alter the molecular function of the p110alpha protein.
nan
Predictive, Oncogenic evidence:
Oncogenic: The abstract discusses how PIK3CA mutations occur almost exclusively in invasive tumors and suggests that these mutations contribute to tumor development by augmenting earlier activation of the PI3K pathway, indicating a role in tumor progression.
Predictive: The abstract mentions that selective inhibition of the alpha isoform of p110 is an attractive therapeutic strategy for late-stage tumors with co-occurring mutations, suggesting that the presence of PIK3CA mutations may correlate with response to specific therapies targeting this pathway.
nan
Diagnostic, Prognostic, Functional evidence:
Diagnostic: The study discusses the frequency of ALK mutations, including R1275, in neuroblastoma tumors, indicating their association with specific genomic and clinical parameters. This suggests that these mutations can be used to classify or define the disease and its subtypes.
Prognostic: The abstract mentions that the presence of certain mutations, including R1275Q, is correlated with poor survival outcomes, indicating that these variants have prognostic significance independent of therapy.
Functional: The abstract states that the R1275Q mutant is characterized by a different degree of autophosphorylation and transforming capacity compared to the F1174L mutant, indicating that this variant alters molecular function.
nan
Predictive, Oncogenic evidence:
Oncogenic: The F1174L mutation is described as having "more potent transforming activity in vivo," indicating its role in tumor development and progression, which aligns with the definition of an oncogenic variant.
Predictive: The F1174L variant is noted to be "responsible for innate and acquired resistance to crizotinib," suggesting that it correlates with treatment response or resistance, which fits the predictive evidence type.
nan
Oncogenic, Functional evidence:
Oncogenic: The study demonstrates that mutations in the ALK gene contribute to tumor development and progression in neuroblastoma, as evidenced by the ability of the mutated kinases to transform NIH3T3 fibroblasts and form tumors in nude mice.
Functional: The abstract indicates that the mutated ALK kinases displayed increased kinase activity compared to the wild-type kinase, suggesting that these mutations alter the molecular function of the protein.
nan
Diagnostic, Prognostic evidence:
Diagnostic: The study mentions the identification of JAK2 V617F in myeloproliferative neoplasias, indicating its role in classifying or confirming the presence of this specific disease subtype.
Prognostic: The abstract discusses the unfavorable prognostic factor associated with IDH1 mutation status in AML, suggesting that similar considerations could apply to JAK2 V617F in the context of myeloproliferative neoplasias, although this is not explicitly stated for JAK2 V617F.
nan
Oncogenic, Functional evidence:
Oncogenic: The abstract discusses that heterozygous somatic mutations in IDH1, including R132H, occur frequently in gliomas and secondary glioblastomas, suggesting that these mutations contribute to tumor development. The presence of these mutations is linked to the dual effects of loss of normal enzyme function and gain-of-function, which are critical for tumorigenesis.
Functional: The abstract mentions that mutations in IDH1, such as R132H, cause loss of normal enzyme function and gain-of-function, leading to the accumulation of D-2-hydroxyglutarate. This indicates that the variant alters the biochemical function of the enzyme, impacting its activity and the metabolic pathways involved.
nan
Functional evidence:
Functional: The study discusses how glutamine is converted to glutamate and further metabolized to alpha-KG, indicating that this biochemical pathway is altered in cells with mutant IDH1. The inhibition of glutaminase and its effects on glutamate and alpha-KG levels demonstrate a change in molecular function related to this variant.
nan
Diagnostic, Prognostic evidence:
Diagnostic: The abstract mentions that mutations in IDH1 were found in a large fraction of young patients and in most patients with secondary GBMs, indicating its role in classifying and defining a subtype of glioblastoma multiforme.
Prognostic: The abstract states that mutations in IDH1 were associated with an increase in overall survival, suggesting that this variant correlates with disease outcome independent of therapy.
nan
Predictive evidence:
Predictive: The abstract indicates that patients with genomic alterations, including mutations, are more likely to respond to targeted therapeutic agents, suggesting a correlation between the variant and treatment response. This aligns with the definition of predictive evidence, as it discusses the relationship between the variant and therapy effectiveness.
nan
Oncogenic evidence:
Oncogenic: The abstract discusses how the deletion of LKB1 affects tumorigenesis and cancer progression, indicating that this somatic variant contributes to tumor development. The mention of its impact on metastasis and cell adhesion further supports its role in oncogenic processes.
nan
Functional evidence:
Functional: The abstract discusses the role of LKB1 and AMPK in regulating various cellular processes, including metabolism and gene transcription, indicating that the variant may alter molecular or biochemical functions related to these pathways.
nan
Diagnostic, Oncogenic evidence:
Diagnostic: The abstract states that LKB1 is causally linked to Peutz-Jeghers syndrome and is one of the most commonly mutated genes in several cancers, indicating its role in defining and classifying disease subtypes.
Oncogenic: The abstract describes LKB1 as a tumor suppressor gene and mentions its involvement in several cancers, suggesting that mutations in LKB1 contribute to tumor development or progression.
nan
Predisposing, Functional evidence:
Predisposing: The abstract states that "mutations in the LKB1 tumour suppressor threonine kinase cause the inherited Peutz-Jeghers cancer syndrome," indicating that these mutations are germline and confer inherited risk for developing this specific disease.
Functional: The abstract discusses how LKB1 interacts with STRAD and MO25, and how this interaction is crucial for its activation and regulation, demonstrating that the variant alters molecular function through its binding properties and activation mechanisms.
nan
Predictive, Prognostic evidence:
Prognostic: The abstract states that "Expression of mutant p53 correlates with poor prognosis in many tumors," indicating that the presence of the mutant variant is associated with disease outcome independent of therapy.
Predictive: The abstract discusses strategies aimed at reactivation of mutant p53 to provide benefits for treatment of tumors resistant to chemotherapy and radiotherapy, suggesting that the variant correlates with response to specific therapies.
nan
Predictive, Prognostic evidence:
Prognostic: The abstract indicates that Ki-ras mutations might affect the survival rate of colorectal cancer (CRC) patients, suggesting a correlation between these mutations and disease outcome. Additionally, it mentions that different types of TP53 mutations could influence the prognosis of patients based on tumor site, further supporting the prognostic nature of these variants.
Predictive: The abstract also discusses the predictive value of TP53 mutations for survival benefit from 5FU chemotherapy, indicating that specific mutations may correlate with treatment response in CRC patients. This suggests that the presence of certain TP53 mutations can influence the effectiveness of a particular therapy.
nan
nan evidence:
Missing abstract
nan
Oncogenic, Functional evidence:
Oncogenic: The study identifies the AKT1 G49A (E17K) and G145A (E49K) mutations as contributing to tumor development in bladder cancer, demonstrating their transforming activity in NIH3T3 cells, which supports their role as oncogenic variants.
Functional: The abstract mentions that the G49A (E17K) and G145A (E49K) mutations enhance AKT activation, indicating that these variants alter the molecular function of the AKT1 protein, which is a key aspect of their functional impact in cancer.
nan
Predictive, Oncogenic evidence:
Oncogenic: The abstract discusses the Akt1 (e17k) mutant as being unstable and sensitive to functional inhibition, indicating that this somatic variant contributes to tumor development or progression through its role in Akt signaling and response to treatment with SC66.
Predictive: The study highlights that the Akt1 (e17k) mutant is intrinsically sensitive to the functional inhibition by SC66, suggesting a correlation between this variant and the response to a specific therapy, which is indicative of predictive evidence.
nan
Prognostic, Functional evidence:
Prognostic: The study reports that patients with tumors harboring the mutant KRas-Gly12Cys variant had worse progression-free survival compared to those with other mutant KRas proteins or wild-type KRas, indicating that this variant correlates with disease outcome independent of therapy.
Functional: The results indicate that the KRas-Gly12Cys variant leads to altered downstream signaling pathways, specifically showing activated Ral signaling and decreased growth factor-dependent Akt activation, which suggests a change in molecular function due to this variant.
nan
Oncogenic evidence:
Oncogenic: The study discusses mutations in the N-ras gene found in patients with cutaneous melanoma, indicating that these mutations contribute to tumor development, particularly in the context of UV damage, which is a known factor in melanoma progression.
nan
Predictive, Diagnostic evidence:
Diagnostic: The study investigates the incidence of BRAF and NRAS mutations in various melanoma subtypes, indicating that these mutations are associated with specific types of melanoma, particularly in mucosal melanomas. This suggests that the presence of these mutations can help classify or define the disease subtype.
Predictive: The abstract mentions the potential for new therapeutic options of anti-RAF treatment for patients with BRAF mutations in cutaneous melanomas, implying that the presence of the BRAF mutation may correlate with response to this specific therapy.
nan
Prognostic evidence:
Prognostic: The study indicates that K-ras mutations correlate with disease recurrence, with a significantly higher prevalence in patients with recurrent disease compared to those who are disease-free, suggesting that these mutations serve as a prognostic factor for disease outcome in colorectal carcinoma.
nan
Oncogenic evidence:
Oncogenic: The abstract states that mutations in the ras genes convert them into active oncogenes, indicating that these somatic variants contribute to tumor development or progression. Additionally, the mention of the high incidence of ras mutations in various tumor types supports their role in oncogenesis.
nan
Diagnostic, Prognostic, Oncogenic evidence:
Diagnostic: The study discusses the association of KRAS mutations with various pathological features in sporadic colorectal cancer, indicating that these mutations are used to classify and understand tumor progression and metastasis in this specific disease context.
Prognostic: The presence of KRAS mutations is correlated with advanced disease features such as wall invasion and the presence of lymph node and distant metastases, suggesting that these mutations may provide information about disease outcome independent of therapy.
Oncogenic: The findings indicate that KRAS mutations contribute to the progression of microsatellite-stable colorectal cancer, demonstrating a role in tumor development and progression.
nan
Oncogenic evidence:
Oncogenic: The study demonstrates that mutations at codon 61 of the human rasH gene lead to increased transforming activity, indicating that these somatic variants contribute to tumor development or progression. The significant variation in transforming potency among the mutants further supports their role in oncogenesis.
nan
Predictive, Diagnostic evidence:
Predictive: The abstract discusses the need for mutation screening to optimize patient selection for treatment with EGFR-targeted therapies, indicating that the presence of specific K-Ras mutations, including Arg164Gln, may correlate with treatment response.
Diagnostic: The abstract mentions the identification of mutations outside previously described hotspot codons, suggesting that these mutations, including Arg164Gln, should be considered in the context of colorectal tumors, which implies a role in defining or classifying the disease.
nan
Oncogenic evidence:
Oncogenic: The abstract states that the N-Ras(G60E) mutation, along with other Ras mutants, exhibited oncogenic properties in biochemical and functional assays, indicating that this variant contributes to tumor development or progression.
nan
Predictive, Diagnostic evidence:
Predictive: The study discusses the efficacy of panitumumab in patients with wild-type KRAS tumors, indicating that the presence of this variant correlates with a better response to therapy, as evidenced by prolonged progression-free survival when combined with chemotherapy. The mention of "wild-type rather than mutant KRAS tumours" highlights the predictive nature of the variant in determining treatment outcomes.
Diagnostic: The abstract states that panitumumab is indicated for use in patients with "wild-type rather than mutant KRAS tumours," which implies that the KRAS variant is used to classify patients for treatment eligibility, thus serving a diagnostic purpose in identifying the appropriate patient population for therapy.
nan
nan evidence:
Missing abstract
nan
Diagnostic, Oncogenic, Functional evidence:
Diagnostic: The study discusses the frequency of p53 mutations in different types of brain tumors, indicating that these mutations are associated with specific tumor subtypes, such as anaplastic astrocytoma and glioblastoma multiforme. This suggests that the presence of these mutations can help classify and define the disease.
Oncogenic: The abstract states that the inactivation of PTEN is associated with glioma progression and confirms its role as a tumor suppressor gene, indicating that PTEN mutations contribute to tumor development. The mention of loss of heterozygosity and the inactivation of both PTEN alleles further supports its oncogenic role in high-grade gliomas.
Functional: The study reports that all detected PTEN missense mutations and an in-frame small deletion inactivated PTEN phosphoinositide phosphatase activity in vitro, demonstrating that these variants alter the molecular function of the PTEN protein.
nan
Functional evidence:
Functional: The study demonstrates that the majority of PTEN missense mutations significantly reduce or eliminate phosphatase activity, indicating that these variants alter the molecular function of the PTEN protein. This is supported by the experimental assays conducted to assess the dephosphorylation capabilities of the mutant proteins.
nan
Predictive, Oncogenic evidence:
Predictive: The study discusses how the BRAF V600E mutation is associated with resistance to BRAF inhibitors and explores the response of BRAF V600E mutated melanoma cells to new compounds (NBDHEX and MC3181), indicating a correlation between the variant and treatment response.
Oncogenic: The BRAF V600E mutation is implicated in the development of melanoma, as the study focuses on its role in tumor progression and resistance mechanisms, demonstrating its contribution to cancer biology.
nan
Prognostic, Oncogenic evidence:
Oncogenic: The study identifies the KRAS(G13D) mutation as an oncogenic mutation found in mycosis fungoides and pleomorphic CTCL, indicating its contribution to tumor development in these malignancies.
Prognostic: The presence of the KRAS(G13D) mutation in stage IV patients correlates with significantly decreased overall survival compared to stage IV patients without mutations, suggesting its role as a prognostic marker in CTCL.
nan
Predictive, Oncogenic evidence:
Oncogenic: The study discusses the coexpression of BRAFV600E in human melanoma cells, indicating that this somatic variant contributes to tumor development and progression, particularly in the context of its interaction with NRASQ61R.
Predictive: The results suggest that the presence of BRAFV600E increases susceptibility to cytotoxicity by T cells, indicating a potential predictive relationship regarding treatment response in melanoma patients harboring this variant.
nan
Prognostic evidence:
Prognostic: The study identifies NRAS mutations as being independently associated with decreased overall survival in patients with stage IV melanoma, indicating that the presence of this variant correlates with a poorer disease outcome. The median survival for patients with NRAS mutations was significantly shorter compared to wild-type patients, supporting its role as a prognostic marker.
nan
Oncogenic evidence:
Oncogenic: The study indicates that the variant, which involves a single nucleotide change substituting lysine for glutamine in position 61 of the N-ras gene, is associated with transforming activity in neuroblastoma cells, suggesting that this somatic variant contributes to tumor development.
nan
Oncogenic evidence:
Oncogenic: The study demonstrates that NRAS mutations in codon 12 or 61 are present in acute myelocytic leukemias (AML) and contribute to tumor development, as evidenced by DNA transfection analyses and tumorigenicity assays. This indicates that these somatic mutations play a role in the progression of myeloid malignancies.
nan
Oncogenic evidence:
Oncogenic: The study discusses NRAS mutations, specifically the glycine to aspartic acid substitution at codon 12, in the context of acute myeloid leukemia (AML) and indicates that these mutations are involved in the neoplastic transformation process, suggesting their role in tumor development. The mention of focus-formation assays further supports the oncogenic nature of these mutations.
nan
Predictive evidence:
Predictive: The abstract discusses how the T315I variant is associated with decreased sensitivity to imatinib and highlights the need for alternative therapies, indicating that this variant correlates with resistance to treatment. The mention of "imatinib-resistant mutants" and the comparative potency of other inhibitors against T315I supports its classification as predictive evidence.
nan
Predictive, Prognostic evidence:
Predictive: The study indicates that the detection of BCR-ABL kinase domain mutations is strongly associated with imatinib resistance, suggesting that these mutations can predict treatment response in chronic myeloid leukemia patients. The mention of "acquired resistance" and the correlation with mutation detection supports this classification.
Prognostic: The results highlight that patients with mutations in the adenosine triphosphate (ATP) binding loop (P-loop) had a median survival of only 4.5 months after mutation detection, indicating that these mutations correlate with poor prognosis independent of therapy. This suggests that the presence of these mutations can serve as a prognostic indicator for patient outcomes.
nan
Diagnostic evidence:
Diagnostic: The study discusses histopathological features associated with pustular drug eruptions, indicating that the observed histological patterns can be used to classify or define the condition. The presence of specific features such as spongiform intraepidermal pustules and leucocytoclastic vasculitis suggests a diagnostic relevance in understanding the disease.
nan
Predictive evidence:
Predictive: The study discusses the response rates to dasatinib treatment in patients with BCR-ABL mutations, noting that high response rates were achieved with different mutations except T315I, indicating that T315I is associated with resistance to dasatinib therapy. This suggests a predictive relationship between the T315I variant and treatment response.
nan
Predictive evidence:
Predictive: The study discusses how EGFR mutations in non-small cell lung cancer (NSCLC) might be predictive for clinical response to EGFR inhibitor treatment, indicating a correlation between mutational status and treatment response. The results also highlight the variability in sensitivity of different EGFR mutations to various inhibitors, further supporting the predictive nature of these mutations in therapeutic contexts.
nan
Predictive, Prognostic evidence:
Predictive: The abstract states that "Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) confer a strong sensitivity to gefitinib," indicating a correlation between EGFR mutations and response to the therapy gefitinib. Additionally, the results show a significant difference in radiographic response rates between patients with EGFR mutations and those with wild-type EGFR, further supporting the predictive nature of these mutations regarding treatment response.
Prognostic: The abstract mentions that "Median survival was not reached for patients with EGFR mutations and was 9.9 months for those with wild-type EGFR," suggesting that the presence of EGFR mutations correlates with improved survival outcomes independent of therapy. This indicates a prognostic role for the EGFR mutations in the context of lung adenocarcinoma.
nan
Predictive, Prognostic evidence:
Predictive: The study indicates that patients with the L858R mutation had a significantly higher response rate to gefitinib treatment (64.7%) compared to those without mutations (13.7%), demonstrating a correlation between the variant and treatment sensitivity.
Prognostic: The results show that patients harboring the L858R mutation experienced significantly prolonged time to progression (TTP) and overall survival compared to those without the mutation, indicating that this variant is associated with better disease outcomes independent of therapy.
nan
Predictive evidence:
Predictive: The study indicates that "EGFR mutations may predict sensitivity to gefitinib," suggesting a correlation between the presence of these mutations and the response to the EGFR kinase inhibitor in patients with non-small cell lung cancer. This aligns with the definition of predictive evidence, as it discusses treatment response related to a specific therapy.
nan
Predictive evidence:
Predictive: The study demonstrates that high EGFR gene copy number and high protein expression are statistically significantly associated with better response to gefitinib therapy, indicating that these factors can predict treatment efficacy in advanced NSCLC. The results show a clear correlation between EGFR status and various treatment outcomes, including response rate and time to progression.
nan
Predictive evidence:
Predictive: The abstract mentions that patients with EGFR-mutant tumors have increased sensitivity to tyrosine kinase inhibitors (TKIs), indicating a correlation between the variant and response to a specific therapy. This suggests that the variant plays a predictive role in treatment outcomes for patients with non-small-cell lung cancer.
nan
Predictive, Diagnostic, Oncogenic evidence:
Predictive: The abstract discusses the predictive effect of EGFR mutations, including L858R, as a good indicator for TKI therapy, indicating that the presence of this variant correlates with treatment response.
Diagnostic: The results section provides specific data on the mutation rate of L858R, suggesting its role in identifying patients who harbor this mutation, which is relevant for diagnosis and treatment decisions.
Oncogenic: The presence of the L858R variant is indicative of its role in tumor development or progression, as it is a well-known somatic mutation associated with non-small cell lung cancer.
nan
nan evidence:
Missing abstract
nan
Predictive, Oncogenic evidence:
Predictive: The abstract states that the T790M mutation "renders gefitinib and erlotinib ineffective inhibitors of EGFR kinase activity," indicating that this variant is associated with resistance to these therapies, which is a predictive context.
Oncogenic: The mention of T790M as a "secondary EGFR mutation" that contributes to resistance in non-small cell lung cancers suggests that it plays a role in tumor progression, aligning with the oncogenic evidence type.
nan
Predictive evidence:
Predictive: The abstract discusses how patients with metastatic cancers who initially benefit from EGFR-targeted therapies eventually develop resistance, indicating a correlation between the variant and resistance to therapy. This suggests that understanding the resistance mechanisms can lead to the development of new therapeutic strategies, highlighting the predictive nature of the variant in relation to treatment response.
nan
Predictive evidence:
Predictive: The study indicates that the presence of EGFR somatic mutations in non-small-cell lung cancer patients is associated with response to treatment with EGFR-tyrosine kinase inhibitors, such as gefitinib and erlotinib. This suggests a correlation between specific mutations and treatment sensitivity, which is a key aspect of predictive evidence.
nan
Predictive, Diagnostic evidence:
Predictive: The study discusses the efficacy of erlotinib in patients with EGFR mutations, including the L858R mutation, indicating that this variant correlates with improved progression-free survival when treated with this specific therapy compared to standard chemotherapy. The mention of "progression-free survival" and the context of treatment response supports this classification.
Diagnostic: The abstract states that patients were selected based on the presence of EGFR mutations, specifically mentioning the L858R mutation, which indicates that this variant is used to classify patients with non-small-cell lung cancer (NSCLC) for treatment eligibility. This aligns with the definition of a diagnostic evidence type, as it confirms the presence of a specific mutation associated with the disease.
nan
Predictive evidence:
Predictive: The study discusses how advanced non-small-cell lung cancer (NSCLC) harboring activating mutations of epidermal growth factor receptor (EGFR) are particularly sensitive to tyrosine kinase inhibitors (TKIs), indicating a correlation between the presence of EGFR mutations and response to treatment with erlotinib and gefitinib. The results show that EGFR TKIs significantly increase the chance of obtaining an objective response compared to chemotherapy, demonstrating predictive evidence for the efficacy of these therapies in EGFR-mutated NSCLCs.
nan
Diagnostic, Functional evidence:
Diagnostic: The abstract discusses the necessity of introducing molecular diagnostics for EGFR-mutated adenocarcinoma, indicating that variants like V689M are used to classify and define a specific disease subtype.
Functional: The results section describes how the V689M variant is constitutively active and stabilizes acceptor/donor interactions, indicating that it alters molecular function.
nan
Predictive evidence:
Predictive: The abstract states that "both these genetic alterations of the EGFR are correlated with high probability to respond to anti-EGFR agents," indicating that the variant is associated with treatment response to specific therapies.
nan
Oncogenic evidence:
Oncogenic: The abstract discusses the role of the EGF receptor (EGFR) family in the development and growth of many types of human tumor cells, indicating that variants in this signaling pathway contribute to tumor development or progression. This aligns with the definition of oncogenic variants as those that drive cancer.
nan
Predictive, Diagnostic evidence:
Predictive: The study discusses the effectiveness of EGFR tyrosine kinase inhibitors (TKIs) in patients with the L858R mutation, indicating a correlation between this variant and treatment response, as evidenced by the reported response rates and progression-free survival.
Diagnostic: The abstract mentions that L858R is one of the well-known EGFR mutations in non-small cell lung cancer (NSCLC), suggesting its role in defining or classifying the disease.
nan
Prognostic evidence:
Prognostic: The BRAF(V600E) mutation was shown to have an independent correlation with the worst outcome for papillary thyroid carcinoma (PTC) patients, indicating that it serves as a poor prognostic factor. The study reported a lower percentage of survivors in the BRAF(V600E)-mutated group, highlighting its impact on patient survival.
nan
Prognostic evidence:
Prognostic: The study indicates that the BRAF(V600E) mutation is associated with poorer outcomes in papillary thyroid cancer (PTC), as evidenced by the increased risk of recurrent and persistent disease, which suggests its role as a prognostic marker. The authors conclude that this mutation is closely related to high-risk clinicopathological factors, reinforcing its prognostic significance.
nan
Functional evidence:
Functional: The study investigates the effect of green tea on iron absorption, indicating that the presence of green tea does not inhibit iron absorption from sodium ferrous citrate tablets. This suggests that the interaction between green tea and iron absorption alters the biochemical function of iron uptake in the body.
nan
Predictive, Oncogenic evidence:
Oncogenic: The abstract discusses BRAF as an important target in cancer due to its presence in 7% of all cancers and its activation by point mutations, indicating its role in tumor development and progression. This aligns with the definition of oncogenic variants contributing to cancer.
Predictive: The mention of single-agent therapy showing efficacy against BRAF mutations suggests a correlation between the variant and response to specific therapies, which supports its classification as predictive evidence.
nan
Predictive, Oncogenic evidence:
Oncogenic: The study discusses how the (V600E)BRAF variant contributes to tumor development by inducing apoptosis in melanoma cells, indicating its role as an oncogene in this context. The evidence is supported by the observation that BRAF depletion leads to increased apoptosis, demonstrating its involvement in cancer progression.
Predictive: The abstract mentions that the inhibition of (V600E)BRAF by the RAF inhibitor Sorafenib induces apoptosis, suggesting a correlation between the presence of this variant and the response to specific therapy. This indicates that the variant may predict sensitivity to treatment with Sorafenib in melanoma cells.
nan
Predictive, Oncogenic evidence:
Predictive: The abstract discusses how BRAFV600E/K is targeted for therapy by the specific inhibitor PLX4032, indicating a correlation between the variant and response to treatment. The mention of PLX4032's effects on BRAFV600E/K cells suggests that the variant is predictive of sensitivity to this therapy.
Oncogenic: The abstract describes BRAFV600E/K as a "frequent mutationally active tumor-specific kinase in melanomas," indicating that this somatic variant contributes to tumor development or progression. The context of its role in melanoma supports its classification as oncogenic.
nan
Oncogenic, Functional evidence:
Oncogenic: The abstract discusses BRAF somatic missense mutations, specifically highlighting that mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells, indicating that these mutations contribute to tumor development or progression.
Functional: The abstract mentions that BRAF is a serine/threonine kinase and that the mutations lead to elevated kinase activity, which alters its molecular function, demonstrating a biochemical change due to the variant.
nan
Predictive evidence:
Predictive: The study assesses the responses of metastatic or locally advanced basal-cell carcinoma to GDC-0449, a small-molecule inhibitor of SMO, indicating a correlation between the variant and treatment response. The results show that 18 out of 33 patients had an objective response to the drug, demonstrating its predictive value in this context.
nan
Functional evidence:
Functional: The study discusses how the p110alpha-R93W mutant leads to increased levels of phospho-AKT(Ser473) compared to wild-type p110alpha, indicating that this variant alters molecular function related to signaling pathways. This suggests a direct impact on the biochemical activity of the protein, which is characteristic of functional evidence.
nan
Diagnostic, Prognostic evidence:
Prognostic: The study reports that patients with PIK3CA mutated tumors, including the H1047R mutation, have significant improvement in overall survival and breast cancer-specific survival, indicating a correlation between the mutation and positive disease outcomes.
Diagnostic: The H1047R mutation is associated with specific clinicopathologic characteristics, such as node negativity, which helps in classifying and understanding the disease subtype in breast cancer patients.
nan
Oncogenic, Functional evidence:
Oncogenic: The study discusses how the E545K mutation in PIK3CA contributes to tumor development by activating the PI3K/AKT pathway and conferring a proliferative advantage in urothelial carcinoma cells, indicating its role in promoting cancer progression.
Functional: The E545K mutation alters the molecular function of PIK3CA by activating downstream signaling pathways, as evidenced by increased AKT activation and enhanced cell motility and migration, demonstrating its biochemical impact on cellular behavior.
nan
Oncogenic evidence:
Oncogenic: The abstract discusses that PIK3CA mutations, including E542K, are associated with increased PI3 kinase activities and contribute to tumor development and progression in head and neck squamous cell carcinomas (HNSCC). The mention of "higher colony forming efficiency, changes in morphology, higher rates of migration and invasion" indicates that these mutations have oncogenic potential.
nan
Oncogenic, Functional evidence:
Oncogenic: The study discusses how fourteen rare cancer-derived mutants of PIK3CA induce oncogenic transformation of chicken embryo fibroblasts, indicating that these somatic variants contribute to tumor development. The evidence of gain of function and activation of signaling pathways further supports their role in oncogenesis.
Functional: The abstract describes how the mutants alter molecular functions, such as enhancing lipid kinase activity and affecting the interaction with other proteins, which demonstrates that these variants have biochemical effects on the protein's activity and function.
nan
Predictive, Diagnostic evidence:
Predictive: The study identifies that models harboring mutations in PIK3CA showed exquisite sensitivity to the antitumor effects of the selective PI3K inhibitor GDC-0941, indicating a correlation between the variant and response to therapy. This suggests that the presence of these mutations can serve as predictive biomarkers for treatment efficacy.
Diagnostic: The abstract mentions the need for additional diagnostic markers, indicating that the study is focused on identifying biomarkers that can classify or define patient populations likely to respond to the PI3K inhibitor. This aligns with the use of variants to confirm or classify disease subtypes in the context of treatment response.
nan
Oncogenic evidence:
Oncogenic: The study discusses gene amplifications at 3q26 in squamous cell lung carcinoma (SCC) and identifies several genes, including PIK3CA, that may be involved in tumor development. This suggests that these somatic variants contribute to the progression of SCC, aligning with the definition of oncogenic evidence.
nan
Predictive, Oncogenic evidence:
Oncogenic: The abstract discusses somatic mutations in the PIK3CA gene and their high frequency in breast and other cancers, indicating that these mutations contribute to tumor development or progression, which aligns with the definition of oncogenic evidence.
Predictive: The mention of PIK3CA mutations as ideal targets for therapeutic development suggests a correlation with response to targeted therapies, indicating predictive evidence regarding treatment sensitivity or resistance.
nan
Predictive evidence:
Predictive: The abstract discusses how the sensitivity of targeted drugs is related to the genetic makeup of individual tumors, indicating that mutational profiles can help prioritize anticancer therapy, which aligns with the predictive nature of the variant's role in treatment response.
nan
Predictive, Functional evidence:
Functional: The study demonstrates that PIK3CA mutations alter the phosphorylation of AKT and transcription factors, indicating a change in molecular function. This is supported by biochemical analyses showing how these mutations affect cellular processes like apoptosis and growth factor dependence.
Predictive: The treatment with the PI3K inhibitor LY294002 preferentially inhibited the growth of PIK3CA mutant cells, suggesting that the presence of these mutations correlates with sensitivity to this specific therapy. This indicates a potential predictive value of PIK3CA mutations in response to PI3K inhibitors.
nan
Oncogenic evidence:
Oncogenic: The abstract discusses the high frequency of alterations in the PI3K pathway and their role in cancer, indicating that these genetic alterations contribute to tumor development. The mention of "oncogenic mechanisms" and "genetic alterations" suggests that the variants discussed are involved in the progression of cancer.
nan
Functional evidence:
Functional: The study demonstrates that the Q60K mutant, along with other PIK3CA mutants, alters the ability to promote cell proliferation and EGF-independent growth, indicating a change in molecular function. Additionally, the ability of different PIK3CA mutants to activate p-AKT and p-p70-S6K further supports the functional impact of these mutations on cellular signaling pathways.
nan
Oncogenic, Functional evidence:
Functional: The abstract discusses how the H1047R mutation in the PIK3CA gene exhibits elevated lipid kinase activity and alters downstream signaling pathways, indicating that it alters molecular function. The study also demonstrates that this mutation contributes to transforming ability in NIH 3T3 cells, further supporting its functional impact.
Oncogenic: The abstract mentions that the H1047R mutation, along with other hotspot mutations, induces morphologic changes and anchorage-independent growth in NIH 3T3 cells, which are indicative of tumor development and progression. This suggests that H1047R contributes to oncogenic processes in the context of colon cancer.
nan
Oncogenic evidence:
Oncogenic: The abstract states that the PIK3CA gene is somatically mutated in several types of human cancer and suggests that these mutations contribute to tumor development, indicating its role as an oncogene. The detection of PIK3CA mutations in various cancers supports the notion that these alterations are involved in cancer progression.
nan
Diagnostic, Oncogenic evidence:
Diagnostic: The study discusses the detection of PIK3CA mutations, including H1047L and H1047R, in various cancers, indicating their association with specific tumor types and mutation frequencies. This suggests that these variants can be used to classify or confirm the presence of disease in patients.
Oncogenic: The mention of PIK3CA mutations in the context of tumor detection implies that these variants, including H1047L and H1047R, contribute to tumor development or progression, as they are found in human tumors across different cancer types.
nan
Diagnostic, Prognostic evidence:
Diagnostic: The study discusses the incidence of PIK3CA amplification in non-small cell lung cancer tissues and its association with specific patient demographics, indicating its role in classifying or defining a subtype of the disease.
Prognostic: The results highlight a significant difference in survival between patients with normal PIK3CA copy number and those with PIK3CA amplification, suggesting that this variant correlates with disease outcome independent of therapy.
nan
Oncogenic, Functional evidence:
Oncogenic: The abstract discusses "recurrent genomic changes in lung tumors" and their "functional role," indicating that these changes contribute to tumor development or progression, which aligns with the definition of oncogenic variants.
Functional: The mention of "better understanding of cell growth, differentiation and apoptotic pathways" suggests that the genomic changes alter molecular or biochemical functions, supporting the classification as functional evidence.
nan
Diagnostic, Oncogenic evidence:
Diagnostic: The study examines the association between PIK3CA gene copy number and tumor development stages, indicating that PIK3CA amplification is frequently observed in various lung cancer subtypes, which suggests its role in classifying or defining these diseases.
Oncogenic: The findings indicate that PIK3CA gene amplification is associated with lung tumorigenesis, suggesting that this somatic variant contributes to tumor development, particularly in squamous and small cell lung cancers.
nan
Functional evidence:
Functional: The study discusses how PIK3CA mutations and copy number gains are associated with increased phosphatidylinositol 3-kinase activity and phosphorylated Akt expression, indicating that these alterations affect molecular function and cell growth. Additionally, the RNA interference-mediated knockdown of PIK3CA inhibited colony formation in cell lines with PIK3CA mutations, further supporting the functional impact of these variants.
nan
Predictive, Diagnostic evidence:
Diagnostic: The study reports that PIK3CA mutations, including E545K, were identified in patients with lung adenocarcinoma, indicating that these mutations can be associated with this specific subtype of cancer.
Predictive: The abstract mentions that the impact of PIK3CA mutations on the efficacy of targeted therapies such as erlotinib and crizotinib is unknown, suggesting a potential correlation with treatment response, which aligns with predictive evidence.
nan
Prognostic evidence:
Prognostic: The study reports that patients with concomitant PIK3CA mutations in exons 9 and 20 experienced significantly worse cancer-specific survival and overall survival compared to wild-type cases, indicating that these mutations correlate with disease outcome independent of therapy.
nan
Oncogenic evidence:
Oncogenic: The abstract discusses mutations in the PIK3CA gene, specifically mentioning H1047R and H1047L, and indicates that these mutations are present in invasive breast carcinoma. The presence of these mutations suggests they contribute to tumor development, which aligns with the definition of oncogenic variants.
nan
Diagnostic, Prognostic, Oncogenic evidence:
Diagnostic: The study investigates the frequency of PIK3CA mutations and amplifications in nasopharyngeal carcinoma (NPC), indicating that PIK3CA gene amplification is associated with advanced tumor stage and lymph node involvement, which helps classify the disease.
Prognostic: The findings show that patients with PIK3CA copy number gain have significantly reduced overall survival time, suggesting that this variant correlates with disease outcome independent of therapy.
Oncogenic: The study highlights that PIK3CA gene amplification is frequent in NPC and is associated with advanced disease, indicating its role in tumor development or progression.
nan
Oncogenic evidence:
Oncogenic: The abstract states that the E542K variant, along with other mutants, is oncogenic in vivo, as it induces tumors in the chorioallantoic membrane of the chicken embryo and causes hemangiosarcomas, indicating its role in tumor development.