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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 evidence:

Missing abstract

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.

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.

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, 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.

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.

Oncogenic evidence:

Oncogenic: The study discusses mutations in the N-ras gene found in patients with cutaneous melanoma, suggesting that these mutations contribute to tumor development, particularly in the context of UV exposure. The mention of mutations being localized at dipyrimidine sites known to be targets of UV damage further supports the notion of these mutations playing a role in tumor progression.

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.

Predictive, Diagnostic, Oncogenic evidence:

Diagnostic: The study investigates the incidence of BRAF and NRAS mutations in various melanoma subtypes, indicating that these mutations are used to classify and define the molecular genetic profiles of different melanoma types, particularly in mucosal melanomas.

Predictive: The mention of "possible new therapeutic options of anti-RAF treatment" for patients with BRAF mutations suggests that these mutations may correlate with response to specific therapies, indicating a predictive relationship.

Oncogenic: The study discusses the unique oncogenetic pathways of tumor development in different melanoma subtypes, implying that BRAF mutations contribute to tumor development in the context of melanoma, which supports the classification as oncogenic.

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.

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.

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.

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.

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.

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.

Oncogenic evidence:

Oncogenic: The abstract states that the N-Ras(G60E) variant, along with other Ras mutants, exhibited oncogenic properties in biochemical and functional assays, indicating its contribution to tumor development or progression.

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 evidence:

Missing abstract

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 evidence:

Missing abstract

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Oncogenic evidence:

Oncogenic: The abstract discusses the involvement of the PIK3CA gene and its common activating missense mutations in a variety of human tumor types, indicating that these mutations contribute to tumor development or progression. This aligns with the definition of oncogenic variants, which are known to drive cancer.

Predictive, Prognostic evidence:

Predictive: The study indicates that PIK3CA mutations were associated with shorter time to progression (TTP) in trastuzumab-treated breast cancer patients, suggesting a correlation with resistance to therapy. This aligns with the definition of predictive evidence, as it discusses the impact of the variant on treatment response.

Prognostic: The presence of PIK3CA mutations was linked to decreased survival from the initiation of trastuzumab treatment, indicating that this variant correlates with disease outcome independent of therapy. This supports the classification as prognostic evidence, as it relates to survival metrics.

Predictive, Prognostic evidence:

Predictive: PIK3CA mutations predicted for longer local recurrence-free survival, indicating a correlation with treatment response or disease outcome based on therapy context.

Prognostic: The study reports that patients with high S-phase fraction had longer recurrence-free survival if they carried mutations in the PIK3CA gene, suggesting that this variant correlates with disease outcome independent of therapy.

Prognostic, Oncogenic evidence:

Oncogenic: The abstract discusses somatic mutations of PIK3CA and their role in the pathogenesis and progression of human breast cancers, indicating that these mutations contribute to tumor development.

Prognostic: The study reports that PIK3CA mutations are significantly associated with a favorable prognosis, demonstrating that the mutation status serves as an independent prognostic factor.

Predictive evidence:

Predictive: The study validates HER2 amplification and PIK3CA mutation as biomarkers for sensitivity to the PI3K inhibitor GDC-0941, indicating a direct correlation between these variants and treatment response in breast cancer models.

Predictive evidence:

Predictive: The study discusses how increased activity of the PI3K pathway in cancer is associated with resistance to chemotherapeutic agents, suggesting that PI3K inhibitors like GDC-0941 could overcome this resistance and enhance the effectiveness of doxorubicin treatment. This indicates a correlation between the variant's activity and the response to therapy, fulfilling the criteria for predictive evidence.

Predictive evidence:

Predictive: The study demonstrates that GDC-0941 sensitizes breast cancer cells to ABT-737, indicating a correlation with enhanced response to therapy when these agents are combined. This suggests that the variant may influence treatment sensitivity, as the combination leads to increased cytotoxicity and apoptosis in breast cancer cells.

Predictive, Functional evidence:

Predictive: The study investigates the pharmacokinetics and activity of GDC-0941, a PI3K pathway inhibitor, in various mouse models, suggesting that the variant's interaction with P-glycoprotein and breast cancer resistance protein may influence treatment response in patients with brain tumors.

Functional: The research demonstrates that GDC-0941 is a substrate of P-glycoprotein and Bcrp1, indicating that the variant alters the molecular function of these transporters, which impacts the drug's brain penetration and pharmacokinetics.

Predictive evidence:

Predictive: The study evaluates the relationship between GDC-0941 plasma concentrations and tumor reduction, indicating that the variant's activation or transforming mutations in the PI3K pathway correlate with the response to this specific therapy. The mention of "tumor pharmacodynamic biomarker" responses and their association with antitumor efficacy further supports this classification.

Predictive evidence:

Predictive: The study discusses the resistance to HER2 inhibitors in breast cancer and investigates the combinatorial activity of GDC-0941, a PI3K inhibitor, with standard therapies, indicating that the variant's presence may correlate with treatment response. The results show that the combination of GDC-0941 with HER2-targeted therapies leads to significant growth inhibition, suggesting a predictive relationship between the variant and therapeutic efficacy.