Predictive, Oncogenic evidence:

Predictive: The study discusses the initiation of combined treatment with BRAF and MEK inhibitors following the identification of the BRAF V600E mutation, indicating that this variant correlates with a positive response to targeted therapy. The significant clinical improvement observed after starting the treatment further supports the predictive nature of this evidence.

Oncogenic: The presence of the BRAF V600E mutation in the context of chemotherapy-refractory extrahepatic cholangiocarcinoma suggests that this somatic variant contributes to tumor development or progression, as it is associated with the patient's cancer diagnosis and treatment decisions.

Predictive, Oncogenic evidence:

Predictive: The study reports that BRAF V600E mutated intrahepatic cholangiocarcinoma (ICC) patients treated with dual BRAF and MEK inhibitors showed excellent clinical and radiological response to therapy, indicating a correlation between the variant and treatment response. The mention of complete and partial responses further supports the predictive nature of this evidence regarding therapy effectiveness.

Oncogenic: The abstract describes BRAF V600E as an oncogenic driver in intrahepatic cholangiocarcinoma, suggesting that this somatic variant contributes to tumor development or progression. The context of its association with advanced-stage ICC reinforces its role in oncogenesis.

Predictive, Diagnostic, Oncogenic evidence:

Predictive: The abstract discusses the patient's excellent tolerance and exceptional response to dual therapy with dabrafenib and trametinib, indicating that the BRAF V600E mutation correlates with a positive therapeutic response, which is a key aspect of predictive evidence.

Diagnostic: The abstract mentions that the patient was diagnosed with BRAF V600E mutant intrahepatic cholangiocarcinoma, indicating that the presence of the V600E variant is used to define and classify the disease, which supports the diagnostic evidence type.

Oncogenic: The variant BRAF V600E is implicated in the development of the poorly differentiated intrahepatic cholangiocarcinoma, suggesting that it contributes to tumor progression, which aligns with the oncogenic evidence type.

Predictive, Diagnostic, Prognostic evidence:

Diagnostic: The study indicates that BRCA1 germline mutations are closely associated with triple-negative breast cancer, suggesting that these mutations can be used to classify or define this specific subtype of cancer.

Prognostic: The results show that BRCA1 impairment is associated with better overall and disease-free survival rates in young women with triple-negative breast cancer, indicating that this variant correlates with disease outcome independent of therapy.

Predictive: The abstract mentions that the findings suggest a significant proportion of young women with BRCA1 deficiency might benefit from PARP inhibitor treatment, indicating a correlation between the variant and response to a specific therapy.

nan evidence:

Parsing error: argument of type 'NoneType' is not iterable

Predictive, Oncogenic evidence:

Predictive: The emergence of the T790M mutation is associated with disease progression after initial response to erlotinib, indicating that this variant may predict resistance to EGFR-targeted therapies. The abstract suggests that the presence of the T790M mutation could follow similar patterns of resistance to EGFR TKIs across different tumor types.

Oncogenic: The T790M mutation is implicated in the progression of the patient's metastatic pancreatic ductal adenocarcinoma, suggesting that it contributes to tumor development or progression. The context of its emergence following treatment indicates its role in the cancer's resistance mechanisms.

Prognostic, Oncogenic evidence:

Prognostic: The study indicates that decreased expression of PBLD is significantly associated with poor tumor differentiation and advanced tumor stage, and that low PBLD expression correlates with worse recurrence-free survival and overall survival in patients with HCC. This suggests that PBLD serves as an independent predictor of patient outcomes, which aligns with the definition of prognostic evidence.

Oncogenic: The findings demonstrate that PBLD inhibits HCC cell growth and invasion in vitro and tumor growth in vivo, indicating that PBLD plays a role in tumor development and progression. This supports the classification of PBLD as an oncogenic variant due to its involvement in cancer-driving behavior.

Prognostic, Functional evidence:

Prognostic: The study indicates that patients with high ANRIL expression had poor overall survival compared to those with low expression, suggesting that ANRIL expression is correlated with disease outcome independent of therapy.

Functional: The loss-of-function experiments demonstrated that decreased expression of ANRIL inhibited cell proliferation, migration, and invasion in cervical cancer, indicating that ANRIL alters molecular functions related to tumor progression.

Predictive, Diagnostic evidence:

Predictive: The study demonstrates that patients with a germline BRCA mutation showed a significantly longer median progression-free survival when treated with olaparib compared to standard therapy, indicating a correlation between the variant and response to the therapy.

Diagnostic: The mention of "germline BRCA mutation" in the context of patient selection for the trial indicates that this variant is used to classify and confirm a specific subtype of breast cancer, thus serving as a diagnostic marker.

Oncogenic, Functional evidence:

Oncogenic: The study describes how the expression of the Ezh2Y641F variant in mouse B-cells or melanocytes leads to high-penetrance lymphoma or melanoma, indicating that this somatic variant contributes to tumor development.

Functional: The results indicate that the Ezh2Y641F variant increases the abundance of global H3K27 trimethylation and causes a widespread redistribution of this repressive mark, suggesting that it alters molecular function related to chromatin structure and gene regulation.

Predisposing, Oncogenic, Functional evidence:

Predisposing: The abstract mentions "germline truncating mutations in DICER1" and states that "mutation carriers are at risk for nonepithelial ovarian tumors," indicating that these mutations confer inherited risk for developing disease.

Oncogenic: The abstract describes how "somatic missense mutations affecting the RNase IIIb domain of DICER1 are common in nonepithelial ovarian tumors" and suggests that these mutations may be oncogenic by altering microRNA processing, which contributes to tumor development.

Functional: The study reports that the "mutant DICER1 proteins had reduced RNase IIIb activity but retained RNase IIIa activity," indicating that the mutations alter the molecular function of the DICER1 protein.

Predictive, Prognostic evidence:

Predictive: The study indicates that additional RAS mutations predicted a lack of response in patients who received panitumumab-FOLFOX4, highlighting the variant's role as a negative predictive biomarker for therapy response. This aligns with the evidence type as it discusses the correlation between the presence of these mutations and treatment outcomes.

Prognostic: The results show that patients with nonmutated KRAS exon 2 who had other RAS mutations experienced inferior progression-free survival and overall survival with panitumumab-FOLFOX4 treatment, indicating that these mutations correlate with disease outcomes independent of therapy. This supports the classification as prognostic evidence.

Predictive, Diagnostic evidence:

Predictive: The study discusses the response rates to the BCL2 inhibitor venetoclax in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma, indicating that certain clinicopathological features, such as fludarabine refractoriness and complex karyotype, are associated with progression on therapy. This suggests a correlation between these factors and treatment outcomes, which aligns with the predictive evidence type.

Diagnostic: The analysis of clinicopathological features to define risk factors for progression and the mention of excluding occult Richter transformation before initiating venetoclax therapy indicate that these factors are used to classify or confirm disease states. This supports the classification of the evidence as diagnostic.

Diagnostic, Prognostic evidence:

Diagnostic: The study revises the diagnosis of primary myelofibrosis (PMF) patients according to modern criteria, indicating that the classification of patients into pre-PMF and overt PMF categories is based on clinical and molecular features, which aligns with the definition and classification of disease subtypes.

Prognostic: The median survival was significantly shortened in overt PMF compared to pre-PMF, with the presence of high mutation risk mutations representing independent predictors of unfavorable outcomes, indicating a correlation with disease progression independent of therapy.

Predictive, Prognostic, Oncogenic evidence:

Predictive: The study discusses the correlation between the reduction of KIT D816V expressed allele burden (EAB) and improved overall survival (OS) in patients treated with midostaurin, indicating that this variant may serve as a predictive biomarker for treatment response.

Prognostic: The reduction of KIT D816V EAB is highlighted as an independent on-treatment marker for improved overall survival, suggesting that this variant has prognostic implications for disease outcome in patients undergoing therapy.

Oncogenic: The abstract mentions that KIT mutations, including D816V, are often involved in the disease evolution of advanced systemic mastocytosis, indicating that this somatic variant contributes to tumor development or progression.

Diagnostic, Predisposing evidence:

Predisposing: The study discusses "familial clustering of myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML) can be caused by inherited factors," indicating that the identified germline variants confer inherited risk for developing these diseases.

Diagnostic: The identification of "pathogenic germ line variant in 5 families (29%)" and the mention of variants "segregating with MDS/AML in 2 families" suggests that these variants are used to classify or confirm the presence of the disease in affected individuals.

Diagnostic, Predisposing evidence:

Predisposing: The study discusses "inherited mutations in RUNX1" that are associated with "familial platelet disorder with propensity to myeloid malignancy," indicating that these mutations confer an inherited risk for developing MDS/AML. The mention of "autosomal dominant syndrome" further supports the classification as predisposing.

Diagnostic: The abstract states that the disorder is characterized by "platelet abnormalities and a predisposition to myelodysplasia (MDS) and/or acute myeloid leukemia (AML)," which implies that RUNX1 mutations are used to define and confirm the diagnosis of FPD/AML. The identification of germline RUNX1 mutations in families with a history of MDS/AML supports its role as a diagnostic marker.

Prognostic evidence:

Prognostic: The abstract states that "TET2 mutation is an unfavorable prognostic factor in patients with intermediate-risk cytogenetics," indicating that the presence of this mutation correlates with poorer disease outcomes independent of therapy. Additionally, it mentions that the negative impact of the mutation is enhanced when combined with other adverse genotypes, further supporting its role as a prognostic marker.

Predictive, Prognostic evidence:

Predictive: The study indicates that the novel PIK3CA mutation p.K944N promotes cell viability in the presence of cetuximab, suggesting a correlation with resistance to this therapy. This aligns with the evidence type as it discusses the variant's role in treatment response.

Prognostic: The results show that patients with PIK3CA or RAS mutations, including p.K944N, detected in ctDNA experienced a pronounced decrease in progression-free survival compared to those without mutations. This indicates that the variant correlates with disease outcome independent of therapy.

Predictive, Functional evidence:

Predictive: The study discusses the correlation between the levels of CDK4 and the sensitivity to palbociclib, indicating that the presence of the mutant CDK4-R24C variant may influence the response to this therapy. This suggests that the variant could be predictive of treatment outcomes with CDK4 inhibitors.

Functional: The results section describes the transfection of cells with a plasmid containing the mutant CDK4-R24C, which implies that this variant alters the molecular function of CDK4. The analysis of mRNA levels in the generated cultures indicates that the variant affects the expression and potentially the activity of the CDK4 protein.

Predictive, Prognostic evidence:

Predictive: The study evaluates the response to erlotinib therapy in patients with HER1/EGFR-expressing non-small-cell lung cancer, indicating that the variant correlates with treatment response. The mention of "predictors of response" further supports the predictive nature of the evidence regarding the variant's role in therapy outcomes.

Prognostic: The results indicate that median survival time and the 1-year survival rate are reported, suggesting that the variant correlates with disease outcome independent of therapy. The mention of "significant predictors of survival" reinforces the prognostic implications of the variant in this context.

Predictive evidence:

Predictive: The study demonstrates that the epidermal growth factor receptor inhibitor erlotinib correlates with improved overall survival and progression-free survival in patients with non-small-cell lung cancer, indicating its predictive value for treatment response. The response rate of 8.9 percent in the erlotinib group compared to less than 1 percent in the placebo group further supports this classification.

Predictive, Diagnostic evidence:

Predictive: The study discusses how gefitinib, an EGFR-tyrosine kinase inhibitor, improved symptoms and induced tumor regressions in patients with NSCLC, indicating a correlation between the variant (EGFR expression) and response to therapy. The mention of symptom improvement and radiographic responses in relation to gefitinib treatment supports this classification.

Diagnostic: The abstract highlights the role of EGFR expression in NSCLC, suggesting that the presence of this variant is used to classify patients who may benefit from gefitinib treatment. This association with a specific subtype of lung cancer aligns with the diagnostic evidence type.

Diagnostic, Prognostic evidence:

Diagnostic: The study examines the expression of EGFR and p53 proteins in non-small cell lung cancer (NSCLC) specimens, indicating their association with tumor characteristics and survival outcomes, which supports their use as biomarkers for disease classification.

Prognostic: The multivariate analysis revealed that EGFR protein expression is a risk factor for survival in NSCLC patients, suggesting that it correlates with disease outcome independent of therapy.

Predictive, Oncogenic evidence:

Predictive: The abstract discusses how BRAF(V600E)-mutant melanoma patients generally benefit from RAF inhibitors like vemurafenib, but some do not respond, indicating a correlation between the variant and treatment response. This suggests that the presence of the V600E variant can influence the effectiveness of specific therapies, making it predictive of treatment outcomes.

Oncogenic: The variant BRAF(V600E) is implicated in driving tumor proliferation in melanoma, as indicated by its association with BRAF-mediated cell proliferation. This supports the classification of the variant as oncogenic, as it contributes to tumor development and progression.

Predictive, Oncogenic evidence:

Predictive: The abstract discusses how BRAF(V600E)-mutant melanoma patients generally benefit from RAF inhibitors like vemurafenib, but some do not respond, indicating a correlation between the variant and treatment response. This suggests that the presence of the V600E variant is predictive of sensitivity or resistance to specific therapies.

Oncogenic: The variant BRAF(V600E) is implicated in tumor development as it is associated with BRAF-mediated cell proliferation in melanoma. The mention of this variant in the context of resistance mechanisms further supports its role in oncogenesis.

Predictive, Oncogenic evidence:

Predictive: The abstract discusses how BRAF(V600E)-mutant melanoma patients generally benefit from RAF inhibitors like vemurafenib, but some do not respond, indicating a correlation between the variant and treatment response. This suggests that the presence of the V600E variant can influence the effectiveness of specific therapies, making it predictive of treatment outcomes.

Oncogenic: The variant BRAF(V600E) is implicated in driving tumor proliferation in melanoma, as indicated by its association with BRAF-mediated cell proliferation. This suggests that the variant contributes to tumor development or progression, classifying it as oncogenic.

Predictive, Oncogenic evidence:

Predictive: The study indicates that the PIK3CA-p.Glu545Lys mutation did not respond to crizotinib, suggesting that this variant may abrogate the response to the therapy. This aligns with the predictive evidence type as it discusses the variant's impact on treatment response.

Oncogenic: The mention of the PIK3CA-p.Glu545Lys mutation in the context of lung adenocarcinomas and its co-occurrence with MET exon 14 skipping mutation suggests a role in tumor development or progression, which supports the oncogenic evidence type.

Predictive, Oncogenic evidence:

Predictive: The study demonstrates that FLT3 mutations correlate with increased sensitivity to the therapy SU11248, as evidenced by the statement that "FLT3 internal tandem duplication (ITD) mutants showed increased sensitivity relative to FLT3-WT." This indicates a relationship between the variant and treatment response.

Oncogenic: The abstract mentions that activating mutations in FLT3 occur in up to 30% of patients with acute myeloid leukemia (AML), suggesting that these mutations contribute to tumor development or progression, which aligns with the definition of oncogenic variants.

Predictive evidence:

Predictive: The abstract states that responses were seen across Bcr-Abl mutants, except T315I, indicating that the presence of the T315I variant correlates with resistance to the therapy bosutinib. This suggests that T315I is predictive of treatment response in patients with chronic myeloid leukemia.

Predictive, Prognostic evidence:

Predictive: The study assesses the predictive role of KIT mutations for response to treatment with the kinase inhibitor sunitinib, indicating that the presence of these mutations correlates with treatment outcomes.

Prognostic: The results indicate that KIT mutations are associated with a significantly shortened survival time in patients with stage IV melanoma, suggesting that these mutations serve as an adverse prognostic factor independent of therapy.

nan evidence:

Missing abstract

Predictive evidence:

Predictive: The study discusses the efficacy of dasatinib in patients with imatinib-resistant chronic myeloid leukemia (CML-AP), indicating that response rates were evaluated in relation to the presence of BCR-ABL mutations, which suggests a correlation with treatment response. The mention of significant hematologic and cytogenetic responses further supports the predictive nature of the variant's role in therapy outcomes.

Predictive, Prognostic evidence:

Predictive: The study discusses the efficacy of dasatinib in patients with chronic myelogenous leukemia in accelerated phase (CML-AP) who are resistant or intolerant to imatinib, indicating that the presence of the BCR-ABL variant correlates with treatment response to dasatinib. The results show significant major and complete hematologic responses, demonstrating the predictive nature of the variant in relation to therapy outcomes.

Prognostic: The study reports on the 12-month progression-free survival and overall survival rates of patients treated with dasatinib, which indicates that the variant's presence correlates with disease outcomes independent of therapy. The overall survival rate of 82% suggests a prognostic implication of the variant in this patient population.

Predictive evidence:

Predictive: The study indicates that EGFR mutations correlate with clinical features of gefitinib response, suggesting that these mutations can predict the likelihood of a positive response to the therapy. The results show a significant difference in response rates to gefitinib based on the presence of EGFR mutations compared to tumors without these alterations.

Predictive, Oncogenic evidence:

Predictive: The abstract mentions that the novel EGFR mutations, including L858R, are "activating mutations responsive to erlotinib," indicating a correlation between the variant and response to a specific therapy. This suggests that the presence of the L858R mutation may influence treatment outcomes with erlotinib.

Oncogenic: The results section discusses the introduction of various mutations, including L858R, into the EGFR coding sequence and their evaluation in vitro, which implies that these mutations contribute to tumor development or progression. The context of assessing the responsiveness of mutant receptors to EGFR inhibitors further supports the oncogenic nature of the L858R variant.

Predictive, Oncogenic evidence:

Predictive: The study discusses how alterations in the EGFR tyrosine kinase domain, including the T790M variant, are associated with erlotinib resistance, indicating that this variant correlates with treatment response and resistance to therapy.

Oncogenic: The presence of the T790M variant is implied to contribute to tumor development or progression, as it is mentioned in the context of 'oncogene addiction' and its role in EGFR signaling, which is critical for cancer cell survival.

Predictive, Oncogenic evidence:

Predictive: The abstract mentions that "most are sensitive to erlotinib and gefitinib," indicating that the L858R variant is associated with a response to these therapies, which classifies it as predictive evidence.

Oncogenic: The results section discusses how various EGFR mutations, including substitutions for L858, contribute to tumor development in lung adenocarcinomas, demonstrating the oncogenic nature of the L858R variant.

Predictive evidence:

Predictive: The presence of the G776insV_G/C mutation in ERBB2 correlates with sensitivity to the HKI-272 therapy, indicating that patients with this mutation may benefit from this specific treatment. The study demonstrates that cells harboring this mutation respond positively to the dual-specific kinase inhibitor, which is a clear indication of predictive evidence.

Predictive, Diagnostic evidence:

Predictive: The study provides evidence that somatic mutations in the EGFR gene's TK domain are associated with sensitivity to gefitinib and erlotinib, as indicated by the significant differences in mutation presence between gefitinib-sensitive and gefitinib-refractory tumors (P = 0.004 and P = 0.003, respectively). This suggests that the presence of these mutations correlates with a positive response to these therapies.

Diagnostic: The abstract mentions that most mutation-positive tumors were adenocarcinomas from "never smokers," indicating a specific association between EGFR mutations and this subtype of lung cancer. This classification helps define a distinct subset of lung cancers based on the presence of these mutations.

Predictive, Diagnostic evidence:

Predictive: The abstract states that mutations of the epidermal growth factor receptor (EGFR) gene in non-small-cell lung cancer (NSCLC) patients predict the patients who will respond to EGFR tyrosine kinase inhibitor (TKI) treatment, indicating a direct correlation between the variant and treatment response.

Diagnostic: The study analyzes EGFR mutations in primary and metastatic tumors, which suggests that these mutations are being used to classify or define the disease state in NSCLC patients, particularly in the context of treatment planning.

Predictive, Oncogenic evidence:

Predictive: The T854A mutation is associated with acquired resistance to EGFR tyrosine kinase inhibitors, specifically gefitinib and erlotinib, indicating that this variant correlates with treatment response. The abstract mentions that the T854A mutation abrogates the inhibition of tyrosine phosphorylation by erlotinib, highlighting its role in resistance to therapy.

Oncogenic: The T854A mutation is described as a second-site acquired resistance mutation in the context of lung adenocarcinoma, suggesting that it contributes to tumor progression and development by enabling resistance to targeted therapies. The identification of this mutation in a patient with EGFR-mutant lung adenocarcinoma supports its role in oncogenesis.

Predictive, Diagnostic, Prognostic evidence:

Predictive: The study indicates that the presence of an EGFR mutation may increase responsiveness to erlotinib, suggesting a correlation between the variant and treatment response. This aligns with the predictive evidence type as it discusses the variant's impact on therapy effectiveness.

Diagnostic: The investigation of EGFR expression and mutations in tumor samples from non-small-cell lung cancer patients suggests that these variants are used to classify and potentially confirm the disease subtype. This supports the diagnostic evidence type as it relates to the association of the variant with the disease.

Prognostic: The results show that survival was longer in the erlotinib group when EGFR was expressed, indicating a correlation with disease outcome independent of therapy. This supports the prognostic evidence type as it discusses survival in relation to the variant without direct therapy context.

Predictive, Diagnostic, Oncogenic evidence:

Predictive: The study indicates that 7 of the 9 responders to gefitinib treatment had EGFR mutations, suggesting a correlation between these mutations and response to the therapy. This highlights the importance of detecting EGFR mutations for therapeutic decision-making in non-small cell lung cancer.

Diagnostic: The abstract mentions that EGFR mutations are detected in non-small cell lung cancer, particularly in adenocarcinoma, which supports the use of these mutations as a biomarker for classifying and confirming the disease subtype. The high mutation rate in adenocarcinoma further emphasizes the diagnostic relevance of these mutations.

Oncogenic: The conclusion suggests that EGFR mutations play an important role in the tumorigenesis of lung adenocarcinoma, indicating that these somatic mutations contribute to tumor development and progression. This is supported by the identification of mutations specifically in tumor tissues from patients with adenocarcinoma.

Predictive, Diagnostic evidence:

Diagnostic: The study indicates that EGFR mutations are significantly associated with adenocarcinoma histology and smoking status, suggesting that these mutations can be used to classify a distinct subset of pulmonary adenocarcinoma. The presence of EGFR mutations in specific patient demographics (e.g., female, never-smokers) further supports their role as a diagnostic marker in lung cancer.

Predictive: The abstract mentions that mutations in the EGFR gene occur in a subset of lung cancer patients showing a dramatic response to EGFR tyrosine kinase inhibitors, indicating that these mutations correlate with treatment response. This suggests that the presence of EGFR mutations can predict sensitivity to specific therapies targeting this pathway.

Predictive, Diagnostic evidence:

Diagnostic: The study identifies EGFR mutations, including the absence of L858R, in a specific subtype of lung cancer (lymphoepithelioma-like carcinomas), indicating that these mutations can be used to classify or define this disease subtype.

Predictive: The mention of the potential benefits of EGFR tyrosine kinase inhibitors for patients with inoperable LELCs suggests a correlation between the presence of EGFR mutations and response to therapy, even though L858R specifically was not present.

Predictive, Diagnostic, Prognostic evidence:

Predictive: The study discusses the association between EGFR mutations, including L858R, and gefitinib treatment response, indicating that gefitinib responsiveness is significantly associated with EGFR mutations. This suggests that the presence of the L858R variant may correlate with the response to gefitinib therapy in NSCLC patients.

Prognostic: The abstract mentions the median survival for responders and non-responders, indicating that the presence of the L858R mutation may correlate with disease outcome, specifically survival, independent of therapy. The reported median survival times for responders and non-responders provide insight into the prognostic implications of this variant.

Diagnostic: The study identifies the L858R mutation as the most common mutation in non-responders, which implies its role in classifying or associating with a specific disease subtype (in this case, non-small cell lung cancer). This suggests that the presence of this mutation can be used to define or confirm the disease in the context of treatment response.

Predictive, Diagnostic evidence:

Diagnostic: The study investigates the presence of EGFR TKD mutations in various subtypes of non-small-cell lung cancer (NSCLC), indicating that these mutations can be used to classify and define specific disease subtypes, particularly in relation to adenocarcinoma components.

Predictive: The conclusion suggests that patients with NSCLC harboring EGFR TKD mutations are considered candidates for molecular therapies targeting EGFR, indicating a correlation between the presence of these mutations and potential treatment options.

Predictive, Oncogenic evidence:

Predictive: The study discusses how the T790M variant is associated with resistance to EGFR inhibitors, indicating that it correlates with treatment response and resistance to therapy. This is highlighted by the mention of AZD9291 overcoming T790M-mediated resistance, which directly relates to the variant's impact on therapy effectiveness.

Oncogenic: The T790M variant is described as a resistance mutation that contributes to disease progression in patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC). This suggests that the variant plays a role in tumor development and progression, aligning with the oncogenic evidence type.

Predictive, Oncogenic evidence:

Predictive: The abstract discusses how mutations in the EGFR kinase domain, including S768I, are associated with clinical responsiveness to gefitinib in patients with non-small-cell lung cancers (NSCLC), indicating a correlation with treatment response.

Oncogenic: The abstract mentions that the S768I mutation, along with other EGFR mutations, contributes to various changes in EGFR's regulatory mechanisms, which may lead to constitutive activation and oncogenesis in NSCLC, suggesting its role in tumor development.

nan evidence:

Missing abstract

Diagnostic evidence:

Diagnostic: The abstract discusses the significant risk for intra-anal HPV-related cancers among gay and other men who have sex with men, indicating that the variant (in this case, the HPV-related cancers) is associated with a specific disease context. This suggests a role in defining or confirming a disease subtype related to anal cancer screening.

Predictive, Diagnostic evidence:

Predictive: The study discusses how EGFR mutation status, including the L858R variant, is associated with sensitivity to treatment with EGFR-tyrosine kinase inhibitors (TKIs) like erlotinib and gefitinib, indicating a correlation with treatment response.

Diagnostic: The mention of EGFR mutation status, including L858R, as a criterion for selecting patients for first-line therapy suggests that this variant is used to classify patients for treatment, thereby serving a diagnostic purpose in the context of non-small cell lung cancer.

Predictive, Functional evidence:

Predictive: The study discusses the pharmacokinetics of dactinomycin and its relationship with toxicity, indicating that patients who experienced any level of toxicity had a higher AUC0-6, suggesting a correlation between the variant (in this case, the dosing or response to dactinomycin) and treatment response or sensitivity to the therapy.

Functional: The pharmacokinetic analysis indicates that the plasma concentrations and exposure levels of dactinomycin are influenced by the administered dose, which suggests that the variant may alter the drug's molecular or biochemical function in the body, particularly in relation to its pharmacokinetics.

Predictive, Diagnostic evidence:

Diagnostic: The study identifies the presence of the L858R mutation in pleomorphic carcinomas, indicating its association with this specific subtype of lung cancer. This suggests that the mutation can be used to classify or confirm the diagnosis of pleomorphic carcinoma.

Predictive: The conclusion mentions that patients with inoperable pleomorphic carcinomas are likely to benefit from treatment with EGFR tyrosine kinase inhibitors, indicating that the presence of the L858R mutation may correlate with response to this specific therapy.

Predictive, Oncogenic evidence:

Predictive: The abstract discusses how the T790M mutation is frequently linked to resistance against first-generation EGFR inhibitors, indicating that this variant correlates with treatment resistance. This suggests that the presence of T790M can predict the response to specific therapies, particularly in the context of lung cancer treatment.

Oncogenic: The T790M mutation is described as an acquired point mutation in the EGFR kinase domain that contributes to resistance mechanisms in lung adenocarcinoma, implying its role in tumor progression. This aligns with the definition of an oncogenic variant, as it is associated with cancer-driving behavior.

Oncogenic evidence:

Oncogenic: The variant 295-298delTCAT is described as a rare sequence alteration in the context of the dihydropyrimidine dehydrogenase (DPD) gene, which is implicated in DPD malfunction. This suggests a potential role in tumor development or progression, particularly in relation to the intolerance to fluoropyrimidine drugs, indicating its relevance in cancer biology.

Predictive, Diagnostic, Oncogenic evidence:

Predictive: The abstract states that "activating mutations of EGFR are found frequently in a subgroup of patients with non-small cell lung cancer (NSCLC) and are highly correlated with the response to gefitinib and erlotinib." This indicates that the variant is associated with treatment response, classifying it as predictive evidence.

Diagnostic: The abstract mentions that "EGFR mutations were found in 102 of the total 349 tumors," suggesting that these mutations are used to classify or define a specific subgroup of NSCLC patients. This supports the classification as diagnostic evidence.

Oncogenic: The abstract discusses the implications of EGFR mutations in the context of tumor development, stating that "a dual genetic change of EGFR can occur in the same allele... which may imply a more selective growth advantage in a cancer cell." This indicates that the variant contributes to tumor progression, classifying it as oncogenic evidence.

Predictive, Diagnostic evidence:

Predictive: The study indicates that patients with EGFR mutations, including the L858R variant, had a significantly better response rate (82%) and longer time to progression (median, 12.6 months) when treated with gefitinib compared to those with wild-type EGFR, demonstrating the predictive value of this variant for treatment outcomes.

Diagnostic: The presence of the L858R mutation is mentioned as part of the broader category of EGFR mutations in patients with non-small-cell lung cancer (NSCLC), which helps classify these patients as having a specific subtype of the disease that is associated with better clinical outcomes when treated with gefitinib.

Predictive, Oncogenic evidence:

Predictive: The study discusses the resistance of the D816V mutation to the kinase inhibitor imatinib mesylate and its sensitivity to the tyrosine kinase inhibitor PKC412, indicating that the variant correlates with response to specific therapies. This suggests that D816V can influence treatment options for c-KIT-positive malignancies.

Oncogenic: The D816V mutation is associated with the transformation of cells in the murine hematopoietic cell line Ba/F3, demonstrating its role in tumor development or progression. This indicates that D816V contributes to oncogenic processes in hematologic malignancies.

Predictive evidence:

Predictive: The abstract mentions that the relapsed thymic carcinoma patient showed a positive response to sorafenib, which indicates that the C-KIT exon 11 mutation correlates with sensitivity to this specific therapy. This suggests that the variant may play a role in predicting treatment response.

Diagnostic, Oncogenic evidence:

Diagnostic: The study evaluates the prevalence of EGFR mutations, including L858R, in thymomas and thymic carcinomas, indicating its potential role in classifying these tumors and exploring targeted therapies. The mention of specific mutations in the context of tumor types supports the diagnostic classification.

Oncogenic: The presence of the L858R mutation in EGFR, a known driver mutation in various cancers, suggests its role in tumor development or progression, particularly in the context of thymomas and thymic carcinomas. This aligns with the oncogenic classification as it indicates a somatic variant contributing to cancer.

Predictive, Diagnostic evidence:

Diagnostic: The abstract mentions that the study evaluated patients with metastatic melanoma "harboring KIT alterations, either mutations or amplifications," which includes the Leu576Pro variant. This indicates that the variant is used to classify or define a specific disease subtype.

Predictive: The study discusses the anti-tumor activity of nilotinib in patients with KIT mutations, including Leu576Pro, and reports treatment responses, indicating a correlation between the variant and response to therapy. This suggests that the variant may influence the effectiveness of the treatment.

nan evidence:

Missing abstract

nan evidence:

Missing abstract

Diagnostic, Oncogenic evidence:

Diagnostic: The study identifies a missense point mutation (Trp557Gly) in KIT exon 11 associated with neurofibromatosis type 1-related GISTs, indicating its role in classifying this specific subtype of tumors.

Oncogenic: The presence of the Trp557Gly mutation in the extramural portion of the largest tumor suggests that this somatic variant contributes to tumor development in the context of GISTs.

Oncogenic evidence:

Oncogenic: The abstract indicates that BRAF mutations (V600E) were found in gastrointestinal stromal tumors (GISTs) that were wild type for KIT and PDGFRA, suggesting that these mutations contribute to the tumor development in this context. The statement about the pathogenetic significance of BRAF mutations in wild type GISTs supports the classification of V600E as an oncogenic variant.

Oncogenic evidence:

Oncogenic: The abstract indicates that BRAF mutations (V600E) were found in gastrointestinal stromal tumors (GISTs) and suggests that these mutations have pathogenetic significance in wild type GISTs, implying that the variant contributes to tumor development or progression.

Predictive, Oncogenic evidence:

Predictive: The study discusses the detection of ALK mutations, including p.C1156Y, in post-treatment tumor samples and highlights their role in crizotinib resistance, indicating a correlation between the presence of this variant and resistance to the therapy.

Oncogenic: The mention of ALK mutations, such as C1156Y, in the context of resistance mechanisms to ALK-TKI suggests that these somatic variants contribute to tumor progression and development, particularly in the setting of non-small cell lung cancer.

Diagnostic, Oncogenic evidence:

Diagnostic: The study discusses ALK gene rearrangements as defining a distinct molecular subset of non-small cell lung cancer (NSCLC), indicating that these rearrangements are used to classify or confirm the disease subtype.

Oncogenic: The presence of ALK rearrangements is implicated in the development of ALK-positive NSCLC, and the study highlights that these rearrangements are associated with resistance to crizotinib, suggesting their role in tumor progression.

Predictive, Oncogenic evidence:

Predictive: The study discusses the efficacy of FLT3 inhibitors (sunitinib and sorafenib) against the D835Y variant, indicating that the sensitivity to these therapies varies based on the specific FLT3 mutations, including D835Y. This suggests a correlation between the presence of the D835Y variant and the response to these treatments, which aligns with the predictive evidence type.

Oncogenic: The abstract mentions that activating mutations in FLT3, including D835Y, are frequent transforming events in acute myeloid leukemia, indicating that this variant contributes to tumor development or progression. This supports the classification of D835Y as an oncogenic variant.

nan evidence:

There are no mentions of variants in the abstract or results section of the study provided. Therefore, no CIViC evidence types can be classified based on the information given.

Diagnostic, Prognostic evidence:

Prognostic: The K-ras codon-12 point mutation was identified as a strong unfavorable prognostic factor, with a significant difference in overall survival and disease-free survival between patients with and without the mutation. This indicates that the presence of the mutation correlates with poorer outcomes independent of therapy.

Diagnostic: The presence of K-ras point mutations is used to define a subgroup of patients with lung adenocarcinoma, indicating its role in classifying the disease and its associated prognosis. This classification is supported by the study's findings that highlight the mutation's prevalence in a specific cancer type.

Prognostic evidence:

Prognostic: The study investigates the prognostic importance of codon 12 K-ras mutations in early-stage non-small-cell lung cancer (NSCLC), noting that for stage II patients, the presence of K-ras mutations was associated with a statistically significant adverse effect on survival, indicating a correlation with disease outcome.

Predictive, Diagnostic, Prognostic evidence:

Diagnostic: The study aims to define patient characteristics associated with K-ras mutation, indicating its potential use as a biomarker for classifying patients with non-small-cell lung cancer (NSCLC).

Prognostic: The results show a strong association between K-ras mutation and decreased patient survival, particularly in stage I tumors, suggesting that this mutation correlates with disease outcome independent of therapy.

Predictive: The study indicates that K-ras codon 12 mutation is a statistically significant predictor of patient survival after adjusting for various factors, highlighting its potential role in predicting treatment outcomes.

Predictive, Prognostic evidence:

Predictive: The study discusses the relationship between mutations in KRAS and PIK3CA and the effectiveness of gefitinib treatment, indicating that tumors with KRAS mutations did not respond to gefitinib, while some with PIK3CA mutations showed a partial response. This suggests that the presence of these mutations can predict the response to gefitinib therapy.

Prognostic: The results indicate that survival was significantly longer in patients with EGFR mutations or in those without KRAS mutations, suggesting that these factors correlate with disease outcome independent of therapy. This highlights the prognostic value of these mutations in lung cancer patients.

Predictive, Prognostic evidence:

Predictive: The study indicates that KRAS mutations are significantly associated with the absence of response to cetuximab therapy, demonstrating that these mutations predict resistance to this treatment.

Prognostic: The overall survival of patients without KRAS mutations was significantly higher compared to those with mutations, indicating that KRAS mutations correlate with worse prognosis independent of therapy.

Predictive, Prognostic evidence:

Predictive: The study indicates that KRAS mutation status is a candidate marker for predicting survival in patients with metastatic colorectal cancer treated with cetuximab, highlighting the correlation between KRAS wild-type status and better overall survival and response to treatment.

Prognostic: The results show that median overall survival was significantly better in KRAS wild-type patients compared to KRAS mutants, indicating that KRAS status correlates with disease outcome independent of therapy.

Prognostic evidence:

Prognostic: The study reports that KRAS mutations in codon 12 and codon 13 are significantly associated with shorter disease-free survival (DFS) in patients with stage III colon adenocarcinoma, indicating that these mutations correlate with disease outcome independent of therapy. The multivariate hazard ratios provided further support the prognostic impact of these mutations on survival.

Predictive, Diagnostic evidence:

Predictive: The study discusses how patients with the KRAS p.G13D mutation are currently excluded from treatment with cetuximab, indicating that the presence of this variant correlates with a lack of response to this therapy. The analysis of progression-free survival and overall survival in relation to the mutation status further supports this predictive evidence.

Diagnostic: The abstract mentions that patients with activating mutations at codon 13 of the KRAS gene are excluded from treatment with certain therapies, which implies that the presence of the p.G13D mutation is used to classify patients regarding their eligibility for cetuximab treatment. This establishes the variant's role in defining a specific patient subgroup in metastatic colorectal cancer.

Predictive evidence:

Predictive: The study discusses the utility of KRAS gene mutation testing in predicting response to anti-EGFR monoclonal antibody therapy, indicating that patients with KRAS mutations in codon 12 or 13 do not benefit from this treatment. This clearly correlates the presence of specific KRAS mutations with resistance to therapy, fulfilling the criteria for predictive evidence.

Predictive, Diagnostic evidence:

Diagnostic: The abstract mentions "greater understanding of the genetic basis of inherited colorectal cancer and identification of patients at risk," indicating that the variant is used to classify or define a disease or subtype.

Predictive: The abstract discusses the importance of "biomarker development... to aid selection of patients likely to respond to therapy," which suggests that the variant correlates with treatment response or sensitivity to specific therapies.

Diagnostic, Oncogenic evidence:

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

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

Prognostic, Oncogenic evidence:

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

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

Predictive, Oncogenic evidence:

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

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

Predisposing, Oncogenic evidence:

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

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

Oncogenic evidence:

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

Predictive, Diagnostic evidence:

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

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

Predictive evidence:

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

Predictive evidence:

Predictive: The study evaluates whether mutation status of k-ras, b-raf, or p53 could predict which patients were more likely to respond to bevacizumab, indicating a focus on the relationship between these variants and treatment response. The mention of hazard ratios for death among patients with different mutation statuses further supports this classification as it relates to therapy outcomes.

nan evidence:

Missing abstract

Predictive, Prognostic evidence:

Prognostic: The study indicates that the BRAF V600E mutation is associated with a significantly higher likelihood of disease progression and death, marking it as a poor prognostic factor independent of treatment regimen. This is supported by the reported hazard ratios for early relapse and death, demonstrating its impact on patient outcomes.

Predictive: The BRAF V600E mutation is mentioned as a predictor for early relapse on first-line therapy, suggesting that it correlates with treatment response. The study discusses the implications of this mutation for patient selection and stratification in clinical trials, indicating its relevance in predicting therapy outcomes.

Predictive, Prognostic evidence:

Predictive: The study indicates that the mutation status of the K-ras gene significantly affects the response to cetuximab treatment, with wild-type K-ras tumors showing improved overall and progression-free survival compared to those with mutated K-ras tumors. This correlation between K-ras mutation status and treatment response classifies the evidence as predictive.

Prognostic: The abstract mentions that the mutation status of the K-ras gene has treatment-independent prognostic value, suggesting that it correlates with survival outcomes regardless of therapy. This aligns with the definition of prognostic evidence, as it indicates the potential impact of K-ras mutation status on overall survival and progression-free survival.

Predictive evidence:

Predictive: The study discusses how BCR-ABL kinase domain point mutations lead to resistance against the ABL kinase inhibitor imatinib, indicating that these mutations correlate with treatment response and resistance to specific therapies. The mention of BMS-354825's effectiveness against imatinib-resistant mutants further supports the predictive nature of these variants in relation to therapy outcomes.

Oncogenic evidence:

Oncogenic: The study identifies a novel double L858R + E884K somatic mutation of the EGFR, indicating that this variant contributes to tumor development or progression in the context of the patient's lung adenocarcinoma. The presence of this mutation is associated with the patient's disease state and treatment resistance, highlighting its role in oncogenesis.

Predictive, Diagnostic evidence:

Predictive: The study discusses the T790M mutation as a secondary mutation that contributes to acquired resistance to gefitinib, indicating a correlation with treatment response. This aligns with the definition of predictive evidence, as it relates to how the presence of the T790M variant affects the efficacy of a specific therapy.

Diagnostic: The T790M mutation is mentioned in the context of identifying tumors with acquired resistance to gefitinib, suggesting its role in classifying or confirming a subtype of non-small cell lung cancer. This supports the diagnostic evidence type, as it is used to define a specific condition related to treatment resistance.

Predictive, Oncogenic, Functional evidence:

Predictive: The abstract discusses a patient with an EGFR mutation who was initially responsive to gefitinib but later relapsed due to a second mutation (threonine-to-methionine) that resulted in gefitinib resistance, indicating a correlation between the variant and treatment response.

Oncogenic: The presence of the threonine-to-methionine mutation is described as contributing to gefitinib resistance, which suggests that this somatic variant plays a role in tumor progression and development in the context of non-small-cell lung cancer.

Functional: The abstract mentions that structural modeling and biochemical studies demonstrated that the threonine-to-methionine mutation alters the response to gefitinib, indicating a change in molecular function related to drug interaction.

Predictive, Diagnostic evidence:

Predictive: The study discusses the use of erlotinib as maintenance therapy for patients with non-small-cell lung cancer (NSCLC) and reports that median progression-free survival (PFS) was significantly longer with erlotinib compared to placebo, indicating a correlation between the EGFR status and response to the therapy. This suggests that the variant related to EGFR may predict sensitivity to erlotinib treatment.

Diagnostic: The study stratified patients by EGFR immunohistochemistry status, indicating that the presence of EGFR protein overexpression is used to classify patients and assess their eligibility for erlotinib treatment. This demonstrates the role of the EGFR variant in defining a specific disease subtype within NSCLC.

Predictive, Oncogenic evidence:

Predictive: The study discusses the response of a patient with a BRAF V600E mutation to vemurafenib, indicating that the presence of this variant correlates with a dramatic therapeutic response, thus providing evidence for its predictive value in treatment outcomes.

Oncogenic: The BRAF V600E mutation is mentioned in the context of contributing to the activity of the mitogen-activated protein kinase pathway in malignant peripheral nerve sheath tumors, suggesting its role in tumor development or progression.

Predictive, Oncogenic evidence:

Predictive: The study discusses how the presence of the BRAF(V600E) variant correlates with the clinical activity of RAF inhibitors in melanoma patients, indicating that this variant is associated with treatment response and resistance mechanisms.

Oncogenic: The evidence presented shows that the BRAF(V600E) variant contributes to tumor development and progression, particularly through its role in dimerization and resistance to RAF inhibitors, which is characteristic of oncogenic behavior.

nan evidence:

Missing abstract

Predictive, Prognostic evidence:

Predictive: The study discusses the response rates to high-dose IL-2 therapy in patients with metastatic melanoma, indicating that baseline performance status and prior systemic therapy are predictive factors for response to treatment. This aligns with the predictive evidence type as it correlates the variant's presence with treatment response.

Prognostic: The results mention that 28% of responding patients remain progression-free, and disease did not progress in any patient responding for more than 30 months, indicating a correlation between the variant and disease outcome independent of therapy. This supports the classification as prognostic evidence.

Predictive, Oncogenic evidence:

Predictive: The study discusses the response rate to the RAF-selective inhibitor PLX4032 in patients with B-RAF(V600E)-positive melanomas, indicating that the presence of this variant correlates with treatment response. The mention of an "80% anti-tumour response rate" highlights the predictive nature of the variant in relation to therapy effectiveness.

Oncogenic: The abstract states that B-RAF(V600E) mutations occur in a significant percentage of melanomas and are implicated in tumor development, which supports the classification of this variant as oncogenic. The evidence of acquired resistance mechanisms further emphasizes its role in tumor progression.

Predictive, Prognostic, Oncogenic evidence:

Predictive: The study demonstrates that the BRAF V600E mutation correlates with improved response rates to the BRAF kinase inhibitor vemurafenib, indicating its predictive value for treatment efficacy in metastatic melanoma.

Prognostic: The results show that patients with the BRAF V600E mutation treated with vemurafenib had significantly improved overall survival rates compared to those treated with dacarbazine, suggesting that this variant is prognostic for better disease outcomes.

Oncogenic: The presence of the BRAF V600E mutation is implicated in the tumor development and progression in melanoma, as evidenced by the improved survival outcomes associated with targeted therapy.