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.

Predictive evidence:

Predictive: The study discusses how trastuzumab treatment correlates with the disruption of HER2/HER3 interactions and leads to antiproliferative effects, indicating that the variant's presence may influence response to therapy. The mention of a selective PI3K inhibitor being effective in combination with trastuzumab further supports the predictive nature of the variant in relation to treatment response.

Oncogenic evidence:

Oncogenic: The abstract discusses that somatic mutations in the PIK3CA gene play a role in tumor initiation, indicating that these mutations contribute to tumor development in breast cancer. The mention of PIK3CA mutations being present in both in situ and invasive breast carcinomas supports the classification of this variant as oncogenic.

Diagnostic, Prognostic evidence:

Diagnostic: The study establishes that IDH1 mutations are a strong genetic marker for distinguishing between secondary glioblastomas and primary glioblastomas, indicating their role in defining and classifying these disease subtypes.

Prognostic: The results indicate that glioblastoma patients with IDH1 mutations have significantly longer survival compared to those without, suggesting that these mutations correlate with better disease outcomes independent of therapy.

nan evidence:

Missing abstract

Diagnostic, Prognostic, Oncogenic evidence:

Prognostic: The study reports that loss of heterozygosity (LOH) 10q is predictive of shorter survival, indicating a correlation between this genetic alteration and disease outcome independent of therapy. The observed survival rates at various time points further support the prognostic implications of the genetic alterations discussed.

Diagnostic: The abstract mentions the frequency of various genetic alterations in glioblastomas, including TP53 mutations, which are used to classify and define the disease subtypes. The association of these mutations with primary and secondary glioblastomas provides evidence for their role in disease classification.

Oncogenic: The presence of TP53 mutations and LOH 10q in glioblastomas suggests that these somatic variants contribute to tumor development and progression, particularly in the context of secondary glioblastomas. The study highlights the different mechanisms of mutation acquisition in these tumor subtypes, reinforcing the oncogenic nature of these alterations.

Prognostic evidence:

Prognostic: The study investigates the relationship between histologic factors and survival in glioblastoma patients, indicating that certain histologic features correlate with patient outcomes, particularly noting the strong negative relationship between advancing age and duration of postoperative survival. This suggests that the variant's presence or absence may influence prognosis independent of therapy.

Diagnostic, Prognostic, Oncogenic evidence:

Prognostic: The abstract discusses median survival times for various glioma types, indicating that the prognosis of diffusely infiltrating gliomas is poorer, with specific survival rates provided for different grades. This correlates the presence of certain genetic alterations, such as TP53 mutations and LOH 10q, with survival outcomes, thus providing prognostic evidence.

Diagnostic: The abstract mentions the frequency of TP53 mutations in different glioma subtypes, which can be used to classify or define these tumors. The association of specific mutations with certain tumor types supports the use of these variants as diagnostic markers.

Oncogenic: The abstract indicates that TP53 mutations and other genetic alterations are frequent in gliomas and discusses their association with tumor characteristics and survival, suggesting that these mutations contribute to tumor development or progression. This aligns with the definition of oncogenic evidence.

Diagnostic, Oncogenic evidence:

Diagnostic: The abstract discusses the distinct disease subtypes of glioblastoma, indicating that primary and secondary glioblastomas are characterized by different genetic pathways and mutation patterns. This classification of glioblastoma based on genetic alterations supports the use of these variants as diagnostic markers for defining and confirming disease subtypes.

Oncogenic: The abstract mentions that TP53 mutations are the most frequent and earliest detectable genetic alteration in the progression to secondary glioblastoma, suggesting that these mutations contribute to tumor development. This indicates that the somatic variants discussed are involved in oncogenic processes related to glioblastoma.

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.

Oncogenic evidence:

Oncogenic: The study provides evidence that RAS oncogenes, specifically K- or NRAS genes activated by point mutation, contribute to tumor development in various types of lung carcinomas, indicating their role in oncogenesis. The detection of activated protooncogenes in the majority of lung tumor DNAs supports the conclusion that these variants are involved in tumor 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.

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, 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.

Predictive, Diagnostic evidence:

Diagnostic: The study discusses the identification of deleterious mutations in moderate-risk breast and ovarian cancer genes and Lynch syndrome genes among patients lacking BRCA1/2 mutations, indicating that these mutations are associated with hereditary breast and/or ovarian cancer (HBOC). This suggests that the presence of these mutations can be used to classify and confirm the risk of disease in individuals, thus supporting their role as diagnostic markers.

Predictive: The findings indicate that the identification of non-BRCA1/2 mutations can lead to changes in clinical management and additional disease-specific screening or prevention measures, suggesting that these mutations correlate with the response to clinical interventions. This highlights the potential for these variants to influence treatment decisions based on their presence.

Diagnostic, Predisposing evidence:

Predisposing: The study discusses the identification of germline BRCA1/2 mutations and other pathogenic variants in genes associated with cancer risk, indicating that these variants confer inherited risk for developing cancer. The mention of "germline-DNA sequencing panel for cancer-risk assessment" supports this classification.

Diagnostic: The study evaluates the performance of a customized sequencing panel for cancer-risk assessment, which is used to identify and confirm pathogenic variants in patients, thereby classifying them based on their genetic mutations. The identification of variants in genes like ATM, BLM, and others suggests their role in defining disease risk.

Predictive, Oncogenic evidence:

Predictive: The study discusses a selective R132H-IDH1 inhibitor (AGI-5198) that blocks the ability of the mutant enzyme to produce R-2-hydroxyglutarate, indicating that the presence of the R132H variant correlates with the response to this specific therapy, as it impaired the growth of IDH1-mutant glioma cells.

Oncogenic: The abstract mentions that the mutant IDH1 (specifically the R132H variant) promotes glioma growth, suggesting that this somatic variant contributes to tumor development or progression.

Predictive, Oncogenic evidence:

Predictive: The study discusses the novel pan-mutant IDH1 inhibitor BAY1436032, which specifically inhibits R-2HG production and induces myeloid differentiation in AML cells carrying IDH1 mutations, including R132G. This indicates a correlation between the presence of the R132G variant and the response to the therapy.

Oncogenic: The abstract mentions that mutations in IDH1, including R132G, contribute to tumor development by leading to the production of the oncometabolite R-2HG, which promotes tumorigenesis through mechanisms such as histone and DNA hypermethylation. This supports the classification of R132G as an oncogenic variant.

Predictive, Oncogenic evidence:

Oncogenic: The abstract discusses somatic gain-of-function mutations in IDH1 and IDH2, indicating that these mutations contribute to tumor development and progression by causing a block in cellular differentiation, which is characteristic of oncogenic behavior.

Predictive: The study highlights that the mutant IDH2 enzyme can be targeted by the inhibitor AG-221, which not only suppresses 2HG production but also induces cellular differentiation in IDH2 mutation-positive AML cells, suggesting a correlation with treatment response.

Predictive, Oncogenic evidence:

Predictive: The study discusses the development of BAY 1436032 as a pan-inhibitor targeting IDH1 mutations, including R132H and R132L, and highlights its ability to significantly prolong survival in mice with tumors carrying the IDH1R132H mutation, indicating a correlation with treatment response.

Oncogenic: The abstract mentions that mutations in codon 132 of IDH1, including R132H and R132L, are frequent in various tumors, suggesting that these somatic variants contribute to tumor development and progression through their neomorphic enzyme activity.

Predictive, Diagnostic evidence:

Predictive: The study demonstrates that IDH mutant (IDHm) intrahepatic cholangiocarcinoma (ICC) cells show a striking response to the multikinase inhibitor dasatinib, indicating a correlation between the IDH mutations and sensitivity to this specific therapy.

Diagnostic: The abstract states that IDH mutations define a distinct subtype of ICC, suggesting that these mutations are used to classify and identify this specific malignancy.

Predictive, Oncogenic evidence:

Oncogenic: The abstract discusses the presence of the IDH1 mutation R132H in a patient with metastatic pancreatic ductal adenocarcinoma (PDA), indicating that this somatic variant is associated with tumor development in this specific cancer type. The mention of the mutation being detected through molecular profiling supports its role in oncogenesis.

Predictive: The abstract notes that the patient received a mutant IDH1 inhibitor (AG-120) as a treatment option, but there was no response. This indicates that the R132H variant was evaluated in the context of therapy, suggesting a predictive relationship regarding treatment response.

Predictive evidence:

Predictive: The study indicates that patients with non-small-cell lung cancer harboring EGFR mutations, including the L858R point mutation, respond well to the EGFR-specific tyrosine kinase inhibitor gefitinib, suggesting a correlation between the presence of this variant and improved treatment outcomes. The results show that gefitinib leads to significantly longer progression-free survival compared to standard chemotherapy, highlighting the predictive nature of the L858R mutation in response to therapy.

Predictive evidence:

Predictive: The study indicates that depletion of Akt3 in triple-negative breast cancer (TNBC) sensitizes cells to the pan-Akt inhibitor GSK690693, suggesting that the variant correlates with sensitivity to a specific therapy. This implies a potential therapeutic target for treatment in TNBC, aligning with the predictive evidence type.

Predictive, Oncogenic evidence:

Predictive: The study discusses the resistance mechanisms to the AKT inhibitor MK2206, indicating that the expression of AKT3 in resistant cells correlates with a loss of sensitivity to this therapy. This suggests that AKT3 plays a role in the response to treatment, making it predictive of resistance to AKT inhibitors.

Oncogenic: The upregulation of AKT3 in AKT inhibitor-resistant breast cancer cells suggests that it contributes to tumor progression and resistance mechanisms, indicating its role as an oncogenic driver in this context.

Predictive, Diagnostic evidence:

Predictive: The study evaluates the efficacy of dovitinib, an FGFR inhibitor, in patients with advanced SCC of the lung whose tumors demonstrated FGFR1 amplification, indicating that the variant correlates with response to a specific therapy. The mention of "overall response" and "disease control rate" further supports this classification as it directly relates to treatment outcomes.

Diagnostic: The study specifies that patients were enrolled based on their tumors demonstrating FGFR1 amplification of > 5 copies, which indicates that this variant is used to classify and confirm a specific subtype of lung cancer. This association with a defined characteristic of the disease supports the diagnostic classification.

Predictive, Oncogenic evidence:

Predictive: The study demonstrates that ATM-deficient MCL cell lines, such as Granta-519 and UPN2, are more sensitive to PARP-1 inhibition, indicating a correlation between the ATM variant status and response to therapy. Additionally, the use of the PARP-1 inhibitor olaparib significantly decreased tumor growth and increased overall survival in mice with ATM-deficient tumors, further supporting the predictive nature of this variant in therapeutic response.

Oncogenic: The characterization of ATM alterations in MCL and the observation that ATM-deficient cells exhibit defective DNA damage signaling and increased sensitivity to treatment suggest that these somatic variants contribute to tumor development and progression in this cancer type. The study's focus on the functional consequences of ATM mutations in the context of cancer supports the classification of these variants as oncogenic.

Oncogenic, Functional evidence:

Functional: The study describes how the CHEK2 mutation p.R474C alters the tertiary structure of the CHK2 protein by disrupting a salt bridge, indicating a change in molecular function. Additionally, the cell-based transfection analysis showed that this variant was unstable and scarcely activated, further supporting its functional impact.

Oncogenic: The conclusion that the homozygous CHEK2 variant p.R474C was contributory in the case of familial cancer suggests that this somatic variant may play a role in tumor development or progression, particularly given the context of multiple primary cancers in the patients.

Diagnostic evidence:

Diagnostic: The abstract discusses the updated recommendations for the diagnosis and management of acute myeloid leukemia (AML), which includes a revised version of the ELN genetic categories. This indicates that the variants are being used to classify or define the disease, aligning with the diagnostic evidence type.

Predictive, Functional evidence:

Predictive: The study indicates that the JAK1S703I mutation is sensitive to treatment with the JAK1/2 inhibitor, ruxolitinib, suggesting a correlation between this variant and therapeutic response. This is supported by the observation that the mutant PDX model showed sensitivity to the treatment, while other non-activating mutants did not.

Functional: The JAK1S703I mutation was shown to activate the JAK-STAT signaling pathway and drive cell proliferation in vitro, indicating that this variant alters molecular function. The introduction of this mutation into cell lines demonstrated its capability to enhance signaling in the absence of cytokine stimulation.

Predictive, Diagnostic evidence:

Predictive: The study assesses the ability of tumor genomic loss of heterozygosity (LOH) to predict response to rucaparib, indicating that LOH high status correlates with a better response to this PARP inhibitor in patients with ovarian carcinoma. This is supported by the findings that progression-free survival was significantly longer in the LOH high subgroup compared to the LOH low subgroup, demonstrating the predictive nature of the variant in relation to treatment outcomes.

Diagnostic: The classification of patients into homologous recombination deficiency subgroups based on tumor mutational analysis, including BRCA mutant and LOH high, indicates that these variants are used to define and classify the disease subtype. This classification is essential for determining the appropriate treatment strategy, thus supporting the diagnostic evidence type.