Diagnostic, Oncogenic evidence:

Diagnostic: The study discusses the correlation between the intermediate-methylation epigenotype and KRAS-mutation((+)), indicating that the presence of this variant can be used to classify or define a specific subtype of colorectal cancer. This association suggests that KRAS mutations are relevant in the context of epigenotype classification in adenomas.

Oncogenic: The mention of KRAS-mutation((+)) in the context of adenoma development implies that this somatic variant contributes to tumor progression, as it is associated with the intermediate-methylation epigenotype in colorectal cancer. This suggests a role for KRAS mutations in the oncogenic process of colorectal carcinogenesis.

Prognostic, Oncogenic evidence:

Oncogenic: The study mentions a single mutation of the BRAF gene (D594G) detected in the context of locally advanced rectal cancer, indicating that this somatic variant may contribute to tumor development or progression.

Prognostic: The results indicate that CIMP positivity correlates with worse disease-free survival outcomes, suggesting that the presence of certain molecular markers, potentially including variants like D594G, may indicate a higher likelihood of poor clinical outcomes.

Predictive, Oncogenic evidence:

Predictive: The abstract mentions that assessing BRAF V600E mutations might help optimize the selection of patients for anti-EGFR monoclonal antibodies, indicating a correlation between the variant and response to therapy.

Oncogenic: The results section describes how the BRAF V600E mutation induces structural changes in the RAF protein that increase its kinase activity, suggesting that this somatic variant contributes to tumor development and progression through the dysregulation of the RAS/RAF/MAPKs signaling pathway.

Predisposing, Oncogenic evidence:

Oncogenic: The abstract discusses how oncogenic mutations in the H-ras, N-ras, or K-ras genes lead to tumor development by disrupting normal signaling pathways, indicating that these somatic mutations contribute to tumorigenesis.

Predisposing: The abstract mentions germline mutations in Ras and other components of Ras signaling pathways that are associated with familial syndromes, suggesting an inherited risk for developing certain diseases.

Oncogenic evidence:

Oncogenic: The study demonstrates that the K-ras codon 12 mutation contributes to tumor development and progression, as evidenced by the more aggressive, invasive, and metastatic characteristics of tumors derived from this mutation compared to those from codon 13. The use of in vitro and in vivo experimental systems to evaluate the tumorogenic capacity further supports the oncogenic nature of the K-ras codon 12 mutation.

Predictive, Diagnostic evidence:

Predictive: The study demonstrates that KRAS mutations correlate with poor response to panitumumab in metastatic colorectal cancer (mCRC), indicating that KRAS status can predict treatment efficacy. The results show a significant difference in progression-free survival (PFS) between wild-type and mutant KRAS groups, supporting the predictive value of KRAS status for therapy response.

Diagnostic: The abstract mentions that KRAS mutations were detected and their status was ascertained in a significant portion of patients, indicating that KRAS status is used to classify patients in terms of their eligibility for panitumumab treatment. This establishes KRAS as a potential diagnostic marker for selecting patients with mCRC for anti-EGFR therapy.

Predictive evidence:

Predictive: The study provides evidence that k-RAS mutations are significantly associated with an absence of response to EGFR tyrosine-kinase inhibitors in NSCLC and anti-EGFR monoclonal antibodies in mCRC, indicating that these mutations serve as predictive biomarkers for resistance to these therapies. The analysis highlights the specificity of k-RAS mutations as negative predictors of treatment response, reinforcing their role in therapeutic decision-making.

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 evidence:

Missing abstract

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.

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.

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.

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.

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.

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.

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.

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.

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 evidence:

Missing abstract

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 evidence:

Missing abstract

nan evidence:

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nan evidence:

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nan evidence:

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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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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 evidence:

Missing abstract

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.

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 evidence:

Missing abstract

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

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.