Predictive, Oncogenic, Functional evidence:

Predictive: The study discusses the KIT V559D mutation in the context of a highly selective inhibitor, CHMFL-KIT-031, which shows potent inhibitory efficacy and anti-tumor activity, indicating that the variant correlates with response to this specific therapy.

Oncogenic: The KIT V559D mutation is described as the most prevalent primary gain-of-function mutation in Gastrointestinal Stromal Tumors (GISTs), suggesting that it contributes to tumor development or progression.

Functional: The abstract mentions that the inhibitor CHMFL-KIT-031 displayed selectivity and efficacy in biochemical assays, indicating that the V559D variant alters molecular or biochemical function related to KIT signaling pathways.

Predictive, Diagnostic evidence:

Diagnostic: The variant Leu858Arg is mentioned in the context of being one of the EGFR mutations used to define the patient population for the study, indicating its role in classifying patients with advanced EGFR-mutation-positive non-small-cell lung cancer (NSCLC).

Predictive: The study compares the efficacy of dacomitinib and gefitinib in treating patients with EGFR mutations, including Leu858Arg, suggesting that this variant is relevant for predicting treatment response in the context of targeted therapies for NSCLC.

Predisposing evidence:

Predisposing: The study discusses germline mutations in candidate genes associated with an increased risk of breast cancer (BC) and ovarian cancer (OC), indicating that these variants confer inherited risk for developing these diseases. The mention of "germline mutations" and the analysis of mutation frequencies in patients supports this classification.

Prognostic, Oncogenic evidence:

Oncogenic: The study discusses the G12D and G12V mutations in KRAS, indicating that these somatic variants are the most frequent mutations found in pancreatic ductal adenocarcinoma (PDAC) and contribute to tumor development, as evidenced by their prevalence in the analyzed tumors.

Prognostic: The results mention a favorable prognosis subset identified through protein profiling, which correlates with specific molecular characteristics, suggesting that the presence of certain KRAS mutations may influence disease outcome.

Predictive, Diagnostic evidence:

Predictive: The study discusses how the presence of intratumor Gammaproteobacteria can induce resistance to the chemotherapeutic drug gemcitabine, indicating a correlation between the bacterial presence and treatment response. This suggests that the variant's influence on drug metabolism is directly related to the efficacy of gemcitabine therapy in pancreatic ductal adenocarcinoma.

Diagnostic: The study reports that 76% of the tested human pancreatic ductal adenocarcinomas were positive for bacteria, indicating an association between the presence of Gammaproteobacteria and the disease. This suggests that the presence of these bacteria could be used as a biomarker for classifying or confirming the disease in patients.

Predictive, Prognostic, Oncogenic evidence:

Oncogenic: The study discusses how mutations in KRAS, specifically in codons G12 and G13, lead to constitutive activation of the KRAS protein, which is associated with uncontrolled cell proliferation and cancer development. This indicates that the G12 and G12D variants contribute to tumor progression in pancreatic cancer.

Predictive: The results indicate that patients with KRAS mutations, including G12 mutations, showed a worse response to gemcitabine-based chemotherapy compared to those with wild-type KRAS, suggesting that these mutations can predict treatment response. Additionally, the study mentions that KRAS mutations could be used as a tool for therapy prediction, further supporting this classification.

Prognostic: The study reports that patients with KRAS mutations had poorer survival outcomes compared to those with wild-type KRAS, indicating that these mutations correlate with disease prognosis independent of therapy. The statistical significance (p = 0.001) reinforces the prognostic value of these mutations in pancreatic cancer.

Predictive, Prognostic evidence:

Predictive: The study discusses how the combination of a YAP inhibitor and LY3009120 enhances sensitivity to treatment in KRAS-mutant pancreatic cancer, indicating a correlation with treatment response. The mention of "increased sensitivity to LY3009120" directly relates to the predictive nature of the variant's response to therapy.

Prognostic: The abstract states that "reduced YAP expression closely correlates with longer relapse-free and overall survival of patients," suggesting that YAP expression levels can serve as a prognostic indicator for patient outcomes independent of therapy.

Predictive, Diagnostic evidence:

Diagnostic: The abstract discusses the lack of a standard screening program for patients at high risk of pancreatic cancer, indicating that certain genetic factors, such as family history and specific mutations, are used to classify individuals at risk for the disease.

Predictive: The abstract mentions that adjuvant chemotherapy with gemcitabine or S-1 is given after surgery, and that FOLFIRINOX and gemcitabine plus nab-paclitaxel are treatments for patients who are not surgical candidates, suggesting that the presence of certain variants may correlate with treatment response in pancreatic cancer.

Predictive, Oncogenic evidence:

Oncogenic: The abstract states that "90% of pancreatic cancer patients harbor somatic oncogenic point mutations in KRAS, which lead to constitutive activation of the molecule," indicating that these mutations contribute to tumor development and progression in pancreatic ductal adenocarcinoma (PDAC).

Predictive: The abstract discusses "targeted therapies directed towards MEK, ERK, PI3K and mTOR" that have shown "promising results for their ability to impede cellular growth or delay tumor formation," suggesting that the presence of KRAS mutations may correlate with response to these therapies.

nan evidence:

Missing abstract

Predictive evidence:

Predictive: The study discusses the efficacy of erlotinib, an EGFR tyrosine kinase inhibitor, in the context of treatment for glioblastoma, indicating a focus on the response to therapy. The mention of improved survival in patients with a specific treatment-related rash further supports the predictive nature of the variant's association with treatment outcomes.

Predictive, Prognostic evidence:

Predictive: The study assesses the efficacy and safety of erlotinib, an EGFR tyrosine kinase inhibitor, in combination with radiation therapy and temozolomide for treating newly diagnosed glioblastoma, indicating a focus on treatment response. The mention of improved survival in patients with a specific rash induced by erlotinib further supports the predictive nature of the variant in relation to therapy outcomes.

Prognostic: The results report median progression-free survival and overall survival rates for patients treated in the study, which correlates with disease outcomes independent of therapy, thus providing prognostic evidence related to the variant's impact on survival.

Prognostic evidence:

Prognostic: The study discusses the impact of genetic aberrations on survival outcomes in patients with myelodysplastic syndromes (MDS), indicating that certain mutations significantly affect survival rates and contribute to a prognostic model that stratifies patients into different risk groups based on their genetic profile. The mention of survival rates associated with these genetic factors supports the classification as prognostic evidence.

Prognostic evidence:

Prognostic: The abstract states that TERT mutations correlate with a poorer outcome in differentiated thyroid tumors, and it specifically mentions that the prognostic value of TERT mutations is significantly stronger than that of BRAF(V600E), indicating that V600E is associated with disease outcome independent of therapy.

Predictive, Diagnostic evidence:

Predictive: The study discusses the response to afatinib treatment in patients with the p.A775_G776insYVMA variant, indicating that this specific mutation may correlate with improved treatment outcomes, as evidenced by a median time-to-treatment failure of 9.6 months and a disease control rate of 100% in this subgroup.

Diagnostic: The identification of the p.A775_G776insYVMA insertion in exon 20 is used to classify patients as having ERBB2 mutation-positive NSCLC, which is crucial for determining eligibility for targeted therapies like afatinib.

Predictive, Diagnostic, Prognostic, Oncogenic evidence:

Oncogenic: The Phe232Cys mutation in CRLF2 is described as a gain-of-function mutation that promotes constitutive dimerization and cytokine-independent growth, indicating its role in tumor development and progression in B-ALL.

Predictive: The study mentions that cells dependent on CRLF2 signaling are sensitive to small molecule inhibitors of JAKs or protein kinase C family kinases, suggesting that the Phe232Cys variant may correlate with response to specific therapies.

Prognostic: The abstract states that CRLF2 overexpression, which includes the Phe232Cys mutation, is associated with poor outcomes in B-ALL, indicating a correlation with disease prognosis.

Diagnostic: The presence of the Phe232Cys mutation in CRLF2 is linked to specific characteristics of B-ALL, which helps in defining and classifying the disease, thus supporting its use as a diagnostic marker.

Oncogenic evidence:

Oncogenic: The study reports the identification of the P2RY8-CRLF2 fusion, which is associated with activating JAK mutations and leads to constitutive Jak-Stat activation and cytokine-independent growth, indicating that these genetic alterations contribute to leukemogenesis in B-progenitor ALL. This suggests that the variant plays a role in tumor development or progression.

Diagnostic, Prognostic evidence:

Diagnostic: The study discusses the classification of gliomas into five molecular groups based on specific alterations, including germline variants, which implies that these variants are used to define or classify the disease. The mention of associations with specific germline variants further supports this classification role.

Prognostic: The results indicate that the molecular groups were independently associated with overall survival among patients with grade II or III gliomas, suggesting that these groups, and thus the variants associated with them, correlate with disease outcome independent of therapy.

Prognostic evidence:

Prognostic: The study discusses the SNP rs2305089 in relation to local recurrence and overall survival in spinal column chordoma, indicating that this variant correlates with disease outcomes independent of therapy.

Prognostic evidence:

Prognostic: The study provides evidence that TERT promoter mutations and ATRX alterations are associated with overall survival in specific groups of infiltrating gliomas, indicating their role in predicting disease outcomes independent of therapy. For instance, the TERT-WT group had significantly worse overall survival than the TERT-MUT group among IDH-mutant 1p/19q-codeleted oligodendrogliomas, demonstrating a clear prognostic implication.

nan evidence:

Missing abstract

Diagnostic, Oncogenic evidence:

Diagnostic: The study provides a complete analysis of KIT mutations in Indian GIST patients, indicating that these mutations, including the Ala-Tyr variant, are associated with the disease, thus serving as a means to classify or define the disease subtype.

Oncogenic: The presence of various KIT mutations, including the Ala-Tyr variant, suggests a role in tumor development or progression, as these mutations are commonly found in GISTs, which are tumors arising from interstitial cells of Cajal.

Predictive, Diagnostic evidence:

Predictive: The study discusses the role of activating mutations in EGFR, including the L858R point mutation, as important markers of response to tyrosine kinase inhibitor (TKI) therapy in non-small-cell lung cancer (NSCLC). This indicates that the presence of the L858R variant correlates with sensitivity to erlotinib treatment, which is a specific therapy.

Diagnostic: The abstract mentions that patients with a confirmed activating mutation of EGFR, including the L858R mutation, were included in the study. This suggests that the presence of the L858R variant is used to define and classify patients as having advanced EGFR mutation-positive NSCLC.

Diagnostic, Oncogenic evidence:

Oncogenic: The study discusses that H3K27M mutations, specifically the lysine 27 to methionine substitution, are recurrent somatic mutations found in approximately 80% of Diffuse Intrinsic Pontine Gliomas (DIPGs), indicating their role in tumor development.

Diagnostic: The presence of the K27M mutation is highlighted as a defining characteristic of DIPGs, which are diagnosed based on the identification of such mutations, thus linking the variant to the classification of this specific tumor type.

Predictive, Diagnostic evidence:

Predictive: The study discusses how the presence of wild-type KRAS significantly improved progression-free survival (PFS) when treated with panitumumab-FOLFOX4 compared to FOLFOX4 alone, indicating that KRAS status correlates with treatment response. The results show a clear relationship between KRAS mutation status and the efficacy of the therapy, which is a hallmark of predictive evidence.

Diagnostic: The study emphasizes the importance of KRAS testing for patients with metastatic colorectal cancer (mCRC), indicating that KRAS status is used to classify patients into different treatment response groups. This classification based on KRAS mutation status aligns with the definition of diagnostic evidence, as it is used to confirm or exclude specific disease subtypes.

Predictive, Diagnostic evidence:

Diagnostic: The EBF1-PDGFRB gene fusion is associated with the Philadelphia-like ALL subtype, indicating its role in classifying and defining a specific disease context within B-cell precursor acute lymphoblastic leukemia (ALL).

Predictive: The study reports that EBF1-PDGFRB-positive patients who are refractory to conventional chemotherapy can achieve a complete response when treated with the tyrosine kinase inhibitor imatinib, suggesting a correlation between the variant and treatment response.

Predictive, Oncogenic evidence:

Predictive: The study discusses the incorporation of the JAK2 inhibitor ruxolitinib into the treatment regimen due to the presence of the F694L mutation, indicating that this variant is associated with a specific therapeutic response aimed at preventing relapse.

Oncogenic: The mention of the F694L mutation in the context of B-precursor acute lymphoblastic leukemia suggests that this somatic variant may contribute to tumor development or progression, as it is being targeted in the treatment strategy.

Predictive, Oncogenic evidence:

Predictive: The study evaluates the sensitivities of ESCC and HNSCC cell lines to HER inhibitors, specifically noting that the presence of the activating EGFR L861Q mutation correlates with hypersensitivity to afatinib, indicating a potential predictive relationship between the variant and treatment response.

Oncogenic: The abstract describes the EGFR L861Q mutation as an "activating" mutation, which suggests that it contributes to tumor development or progression, supporting its classification as oncogenic.

Predictive, Oncogenic evidence:

Oncogenic: The study identifies somatic mutations in the ERBB4 gene that contribute to increased kinase activity and transformation ability, indicating that these mutations play a role in tumor development in melanoma.

Predictive: The findings suggest that melanoma cells with mutant ERBB4 exhibit reduced cell growth when treated with the ERBB inhibitor lapatinib, indicating a correlation between the variant and response to therapy.

Predictive, Oncogenic evidence:

Predictive: The study discusses the selective killing of leukemic cells bearing the MLL gene translocation upon treatment with EPZ004777, indicating a correlation between the presence of this variant and response to the therapy. Additionally, the in vivo administration of EPZ004777 leading to extended survival in a mouse model further supports the predictive nature of this variant in relation to treatment outcomes.

Oncogenic: The abstract mentions that mislocated enzymatic activity of DOT1L is proposed as a driver of leukemogenesis in mixed lineage leukemia (MLL), indicating that the variant contributes to tumor development or progression. The selective inhibition of H3K79 methylation in MLL cells suggests that the variant plays a role in the oncogenic process associated with this leukemia subtype.

Diagnostic, Functional evidence:

Diagnostic: The study discusses chromosomal rearrangements of the MLL/KMT2A gene as being associated with various types of acute leukemias, indicating that these rearrangements can be used to classify or define the disease in patients. The identification of specific gene fusions and their correlation with different age groups further supports the diagnostic relevance of these variants.

Functional: The molecular characterization of MLL breakpoints and their correlation with clinical outcomes suggests that these variants alter the molecular function of the MLL gene, impacting its role in leukemia. The study implies that understanding these breakpoints can lead to insights into the functional domains of the MLL gene.

Predictive, Oncogenic evidence:

Predictive: The study indicates that somatic ERCC2 mutations correlate with complete response to cisplatin-based chemotherapy, suggesting that these mutations may inform the usage of cisplatin-containing regimens in muscle-invasive urothelial carcinoma. This highlights the predictive nature of the variant in relation to treatment response.

Oncogenic: The mention of somatic ERCC2 mutations and their role in contributing to cisplatin sensitivity implies that these mutations may play a part in tumor development or progression, particularly in the context of chemotherapy response. This supports the classification of the variant as oncogenic.

nan evidence:

Missing abstract

nan evidence:

Missing abstract

Diagnostic evidence:

Diagnostic: The study discusses the potential of P16 INK4a gene promoter methylation detection as a biomarker for diagnosing non-small cell lung cancer (NSCLC), indicating its role in defining or confirming the disease. The mention of "biomarker for NSCLC diagnosis" supports its classification as diagnostic evidence.

Predictive, Diagnostic, Predisposing evidence:

Diagnostic: The study identifies coding germline IKZF1 variation in familial childhood ALL and sporadic B-ALL, indicating that these variants are used to classify and confirm the disease in affected individuals.

Predictive: The abstract mentions that the majority of variants adversely affected IKZF1 function and drug responsiveness of leukemic cells, suggesting a correlation between these variants and decreased sensitivity to therapies, particularly tyrosine kinase inhibitors.

Predisposing: The identification of germline IKZF1 variation in familial childhood ALL supports the notion that these variants confer inherited risk for developing the disease, as they are explicitly described as germline.

Predictive, Diagnostic, Oncogenic evidence:

Predictive: The study discusses how the KRAS G13D mutation may influence the response to cetuximab therapy in patients with metastatic colorectal cancer, indicating a potential correlation between the variant and treatment outcomes. The abstract specifically mentions that patients with tumors harboring the G13D mutation may benefit from cetuximab, which aligns with predictive evidence regarding therapy response.

Diagnostic: The mention of "patients with chemotherapy-refractory KRAS G13D mutation-positive mCRC" indicates that the G13D variant is used to classify and define a specific subtype of metastatic colorectal cancer, supporting its role as a diagnostic marker. This classification is essential for selecting appropriate treatment strategies for these patients.

Oncogenic: The context of the study focuses on the KRAS G13D mutation in relation to metastatic colorectal cancer, suggesting that this somatic variant contributes to tumor development or progression. The study's emphasis on the mutation's role in a specific cancer subtype supports its classification as oncogenic.

Predictive, Oncogenic evidence:

Predictive: The study discusses the emergence of the PDGFRBC843G mutation, which "directly conferred resistance to all generations of ABL TKIs," indicating that this variant is associated with treatment resistance to specific therapies.

Oncogenic: The identification and functional characterization of the AGGF1-PDGFRB fusion gene and the PDGFRBC843G mutation demonstrate their roles in driving leukemia progression, which supports the classification of these variants as oncogenic.

nan evidence:

Missing abstract

Predictive, Diagnostic, Prognostic, Oncogenic evidence:

Predictive: The study discusses the efficacy of dabrafenib and trametinib combination therapy specifically in patients with BRAF V600E-mutated anaplastic thyroid cancer, indicating a correlation between the presence of the V600E mutation and the response to this therapy. The mention of a 69% overall response rate further supports the predictive nature of this evidence regarding treatment response.

Diagnostic: The variant BRAF V600E is used to define and classify the specific subtype of anaplastic thyroid cancer being studied, as the therapy was administered to patients with predefined BRAF V600E-mutated malignancies. This indicates that the presence of the V600E mutation is integral to the diagnosis and classification of this cancer type.

Prognostic: The study reports on overall survival and progression-free survival estimates for patients with BRAF V600E-mutated anaplastic thyroid cancer, independent of therapy, suggesting that the presence of this variant may correlate with these disease outcomes. The 12-month estimates of survival rates provide prognostic information related to the variant.

Oncogenic: The BRAF V600E mutation is known to contribute to tumor development and progression, and its presence in anaplastic thyroid cancer suggests an oncogenic role. The study's focus on this specific mutation in the context of a cancer type further supports its classification as oncogenic.

Diagnostic, Oncogenic evidence:

Diagnostic: The abstract states that nearly 80% of DIPGs harbor a K27M mutation, indicating its association with this specific disease and suggesting its role as a biomarker for classification.

Oncogenic: The results section discusses the frequent histone 3 mutations (K27M-H3) in DIPG, suggesting that these mutations may be important drivers of tumor development, which aligns with the definition of oncogenic variants.

Predictive, Diagnostic, Oncogenic evidence:

Predictive: The study identifies EGFR extracellular domain mutations that mediate resistance by blocking the binding of anti-EGFR antibodies, indicating a correlation between these mutations and treatment resistance. This suggests that the presence of these mutations can predict how patients will respond to anti-EGFR therapies.

Diagnostic: The analysis of cfDNA profiling effectively defines the genomic landscape of cancer, which includes identifying specific mutations such as those in the EGFR ECD. This indicates that these mutations can be used to classify or confirm the presence of certain disease characteristics in colorectal cancer patients.

Oncogenic: The presence of EGFR ECD mutations is associated with tumor heterogeneity and resistance mechanisms, suggesting that these mutations contribute to tumor development or progression in colorectal cancer. This aligns with the definition of oncogenic variants that drive cancer behavior.

Diagnostic, Prognostic evidence:

Prognostic: The study indicates that the common polymorphism rs2853669 modifies the effect of TERT promoter mutations on survival and tumor recurrence, with specific hazard ratios reported for patients with and without the variant allele. This suggests that the variant is associated with disease outcomes, making it relevant for prognosis.

Diagnostic: The abstract discusses the association of the TERT promoter mutations with patient survival and disease recurrence, indicating that the presence of the polymorphism rs2853669 can serve as a marker for classifying patient outcomes in urothelial cell carcinoma. This aligns with the diagnostic evidence type as it relates to defining disease characteristics.

Predisposing evidence:

Predisposing: The study identifies germline mutations in cancer-predisposing genes in 8.5% of children and adolescents with cancer, indicating that these mutations confer inherited risk for developing cancer. The mention of "germline mutations" and the context of cancer predisposition clearly supports this classification.

Predisposing, Functional evidence:

Predisposing: The study discusses germline mutations in the TP53 gene, which are associated with the Li-Fraumeni syndrome, indicating that these inherited mutations confer an increased risk for developing adrenocortical carcinoma (ACC) in children. The mention of family history and risk for multiple primary malignancies further supports the classification as predisposing.

Functional: The study includes a functional analysis of novel TP53 variants, demonstrating a wide range of mutant protein function and its correlation with clinical outcomes, which indicates that these variants alter molecular or biochemical function. The analysis of how different mutations affect protein functionality aligns with the functional evidence type.

nan evidence:

Missing abstract

Predictive, Oncogenic evidence:

Predictive: The abstract mentions that "PI3K pathway activation resulting from PTEN loss or PIK3CA mutations may lead to drug resistance to lapatinib and trastuzumab," indicating that the E9R variant is associated with resistance to specific therapies.

Oncogenic: The context of PIK3CA mutations, including E9R, in relation to HER2-positive breast cancer suggests that these mutations contribute to tumor development or progression, aligning with the oncogenic evidence type.

Diagnostic, Predisposing evidence:

Diagnostic: The study discusses the prevalence of germline RET mutations, including Val804Met, in families with hereditary medullary thyroid carcinoma (MTC), indicating that this variant is used to classify and confirm the presence of the disease. The mention of the variant's frequency in the context of hereditary MTC supports its role as a diagnostic marker.

Predisposing: The abstract specifies that Val804Met is a germline mutation associated with multiple endocrine neoplasia type 2 (MEN 2), which indicates that it confers inherited risk for developing this disease. The context of the study focuses on hereditary cases, reinforcing the predisposing nature of this variant.

Predictive evidence:

Predictive: The abstract discusses how the BCR-ABL1(T315I) mutant confers high-level resistance to tyrosine kinase inhibitors (TKIs), including ponatinib, and mentions that in vitro resistance profiling was predictive of treatment outcomes in Philadelphia chromosome-positive leukemia patients. This indicates a correlation between the variant and resistance to specific therapies.

Predictive evidence:

Predictive: The abstract discusses the efficacy of ponatinib against the BCR-ABL1T315I variant, indicating that this variant is associated with treatment response in patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) who are resistant or intolerant to other therapies. The mention of achieving major cytogenetic and molecular responses further supports the predictive nature of this evidence.

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 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.

nan evidence:

Missing abstract

Predictive, Diagnostic, Oncogenic evidence:

Predictive: The abstract states that the EGFR T790M mutation is associated with resistance to the standard treatment, osimertinib, indicating that this variant correlates with treatment response and resistance.

Diagnostic: The results section mentions that EGFR T790M is the most frequent mechanism of resistance in lung tumors, suggesting that this variant is used to classify or define a specific subtype of non-small cell lung cancer (NSCLC) associated with acquired resistance to EGFR-TKIs.

Oncogenic: The presence of the EGFR T790M mutation is implicated in the development of resistance mechanisms in lung tumors, indicating that it contributes to tumor progression and behavior in the context of cancer.

Oncogenic evidence:

Oncogenic: The study demonstrates that the deletion of Trp53, in combination with other genetic alterations, contributes to tumor development in a mouse model of clear cell renal cell carcinoma (ccRCC). The results indicate that mice with Trp53 deletion developed a higher incidence and number of tumors, supporting the role of this variant in tumor progression.

Prognostic, Oncogenic evidence:

Prognostic: The study reports that reduced SHP-1 expression is associated with shorter overall survival of patients with HCC, indicating its potential role as a prognostic biomarker for disease outcome.

Oncogenic: The knockout of Ptpn6 in hepatocytes enhanced hepatocarcinogenesis and metastasis of primary liver cancer in mice, suggesting that SHP-1 contributes to tumor development and progression.

Predictive, Oncogenic, Functional evidence:

Predictive: The study demonstrates that the EGFR L718V mutation mediates resistance to osimertinib while retaining sensitivity to afatinib, indicating its role in predicting treatment response.

Oncogenic: The identification of the L718V mutation as a newly acquired mutation in conjunction with other EGFR mutations suggests its contribution to tumor progression and resistance mechanisms in non-small cell lung cancer.

Functional: In vitro studies showed that the L718V mutation alters the response to different EGFR TKIs, indicating a change in molecular function related to drug sensitivity and resistance.

Prognostic evidence:

Prognostic: The study indicates that the presence of p53 mutations is associated with a significantly shorter survival period for patients with non-small-cell lung cancer (NSCLC), particularly in those with advanced disease stages, as demonstrated by the univariate and multivariate analyses which found independent prognostic significance for p53 mutations.

Predictive, Prognostic evidence:

Predictive: The study discusses how the T315I mutation correlates with resistance to nilotinib and dasatinib therapies, indicating that the presence of this mutation can predict treatment failure when these inhibitors are used. The mention of "resistant mutations" and their impact on therapy selection highlights the predictive nature of the variant in the context of treatment response.

Prognostic: The results indicate that patients with the T315I mutation had significantly lower failure-free survival rates compared to those with other mutations or no mutations, suggesting that this variant is associated with poor disease outcomes independent of therapy. The specific survival rates provided reinforce the prognostic implications of the T315I mutation in chronic myeloid leukemia.

Predictive, Prognostic evidence:

Predictive: The abstract mentions that the T315I mutant has proven particularly difficult to target, indicating that this variant is associated with resistance to tyrosine kinase inhibitors (TKIs), which directly relates to treatment response.

Prognostic: The abstract discusses the "prognostic implications of BCR-ABL1 KD mutations," suggesting that the presence of the T315I variant may correlate with disease outcomes in patients with chronic myeloid leukemia, independent of therapy.

Diagnostic evidence:

Diagnostic: The abstract discusses the importance of standardizing the interpretation and reporting of molecular results, which implies that variants are used to classify or define diseases or subtypes in cancer testing. The mention of a four-tiered system to categorize somatic sequence variations based on their clinical significance further supports this classification.

Predictive, Oncogenic evidence:

Predictive: The study discusses how the HER2T798I mutation is associated with acquired resistance to neratinib, indicating that this variant correlates with treatment response and resistance to a specific therapy. The mention of neratinib and the implications of the mutation on drug binding further supports its predictive nature regarding therapy outcomes.

Oncogenic: The HER2T798I mutation is described as an acquired mutation that contributes to resistance in a patient with HER2-mutant breast cancer, suggesting its role in tumor progression and development. The context of this mutation arising in a cancer setting reinforces its classification as oncogenic.

Predictive evidence:

Predictive: The abstract discusses how certain toxicities associated with targeted therapies correlate with response to treatment, indicating that genetic polymorphisms can influence drug response. This suggests that the variant may be predictive of how a patient will respond to specific therapies based on their genetic makeup.

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.

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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, 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.