Predictive, Prognostic, Oncogenic evidence:

Oncogenic: The study discusses STAG2 mutations as contributing to tumor progression in Ewing sarcoma, indicating that these somatic variants play a role in the development of the disease.

Prognostic: The findings reveal that STAG2 and TP53 mutations are associated with poor outcomes in patients, suggesting that these variants correlate with disease prognosis independent of therapy.

Predictive: The mention of the need for alternative therapies for tumors harboring STAG2 mutations implies a correlation between these mutations and resistance to current treatments, indicating a predictive relationship.

Diagnostic, Oncogenic evidence:

Oncogenic: The study discusses the loss of STAG2 expression in Ewing sarcoma tumors, indicating that this somatic variant is associated with disease dissemination, which suggests its role in tumor progression. The mention of STAG2 loss occurring through point mutation and rearrangement further supports its contribution to oncogenic processes in this cancer type.

Diagnostic: The abstract states that STAG2 loss is present in more than 15% of Ewing sarcoma tumors and is associated with disease dissemination, indicating its potential use as a biomarker for classifying or confirming the disease. This association with a specific subtype of Ewing sarcoma highlights its relevance in diagnostic contexts.

Oncogenic evidence:

Oncogenic: The study reports a high frequency of mutations in the beta-catenin gene in sporadic hepatoblastomas, indicating that these activating mutations contribute to tumor development in this context. The evidence suggests that the mutations lead to the accumulation of beta-catenin protein, which is associated with tumorigenesis.

Diagnostic evidence:

Diagnostic: The study discusses the association of CTNNB1 mutations with sporadic desmoid tumors, indicating that these mutations can be used as a specific diagnostic tool for distinguishing desmoid tumors from other similar lesions. This aligns with the definition of a diagnostic evidence type, as it confirms the role of the variant in classifying a disease.

nan evidence:

Missing abstract

Diagnostic, Prognostic evidence:

Diagnostic: The study discusses the prevalence of CTNNB1 mutations, including T41A, in sporadic desmoid tumors, indicating that these mutations are associated with the disease. The mention of mutation status correlating with disease outcome further supports its role in defining the disease context.

Prognostic: The results indicate that patients with beta-catenin-mutated tumors, including those with the T41A variant, had a slightly worse 5-year recurrence-free survival compared to those with wild-type tumors, suggesting a correlation with disease outcome independent of therapy.

Predictive, Functional evidence:

Predictive: The Gly101Val mutation in BCL2 is associated with acquired resistance to the BCL2 inhibitor venetoclax, as it significantly reduces the drug's binding affinity, which correlates with clinical disease progression in patients. This indicates that the variant can predict treatment response and resistance to therapy.

Functional: The Gly101Val mutation alters the molecular function of BCL2 by reducing its affinity for venetoclax by approximately 180-fold, which prevents the drug from effectively displacing pro-apoptotic mediators. This change in binding dynamics demonstrates a clear alteration in biochemical function due to the variant.

Predictive, Oncogenic evidence:

Predictive: The study discusses the efficacy of RXDX-105, a small molecule inhibitor that targets BRAF, suggesting that it may improve treatment outcomes for neuroblastoma, particularly in relation to the BRAF(V600E) variant. This indicates a correlation between the variant and response to therapy, aligning with the predictive evidence type.

Oncogenic: The mention of BRAF(V600E) in the context of a novel inhibitor with antitumor activity implies that this somatic variant contributes to tumor development or progression, which is characteristic of oncogenic evidence.

Predictive evidence:

Predictive: The study discusses the efficacy of gefitinib combined with chemotherapy in patients with EGFR mutations, indicating that the presence of these mutations correlates with improved progression-free survival (PFS) and overall survival (OS) when treated with this combination therapy compared to gefitinib alone. This suggests that the EGFR mutations are predictive of a better response to the combined treatment approach.

Predictive evidence:

Predictive: The study discusses the impact of an EGFR-sensitizing mutation on the response to therapy, specifically noting that adding pemetrexed and carboplatin to gefitinib significantly improved progression-free survival (PFS) and overall survival (OS) in patients with advanced non-small-cell lung cancer (NSCLC). This indicates a correlation between the variant and treatment response, fulfilling the criteria for predictive evidence.

Predictive, Diagnostic evidence:

Predictive: The study discusses the antitumor activity of lorlatinib in ROS1-positive non-small-cell lung cancer (NSCLC), indicating that the presence of the ROS1 variant correlates with the response to this specific therapy. The results show objective responses in both TKI-naive patients and those previously treated with crizotinib, highlighting the variant's role in predicting treatment efficacy.

Diagnostic: The abstract mentions that patients were enrolled based on having histologically or cytologically confirmed advanced ROS1-positive NSCLC, indicating that the ROS1 variant is used to classify and confirm the disease subtype. This association underscores the importance of the variant in diagnosing this specific type of lung cancer.

Predictive evidence:

Predictive: The study discusses how the NRAS Q61K variant is involved in trametinib resistance in neuroblastoma, indicating that this variant correlates with the response to therapy, specifically the MEK1/2 inhibitor trametinib. The findings suggest that YAP1 activity influences the sensitivity of RAS-driven neuroblastomas to trametinib, highlighting the predictive nature of the variant in the context of treatment response.

Predictive, Oncogenic evidence:

Predictive: The study indicates that the G660D variant is associated with a remarkable clinical response to HER2 blockade in a lung cancer patient, suggesting that this variant correlates with sensitivity to specific therapies targeting HER2.

Oncogenic: The abstract describes how the G660D mutation contributes to HER2 activation through asymmetric kinase dimerization, indicating its role in tumor development or progression.

Predictive, Oncogenic evidence:

Predictive: The study indicates that ERBB2 mutations predict a greater response to lapatinib, as sensitivity to the drug was greatest among cell lines with these mutations. This suggests a correlation between the presence of ERBB2 mutations and the effectiveness of lapatinib treatment in advanced urothelial bladder cancer.

Oncogenic: The abstract mentions that ERBB2 mutations impact UBC proliferation and signaling, which implies that these mutations contribute to tumor development or progression. The enhanced phosphorylation and activation of ErbB2 in mutated cell lines further supports the oncogenic role of these variants.

Oncogenic evidence:

Oncogenic: The variant NRAS (Q61L) is mentioned in the results section in the context of the HL-60 cell line, which indicates its potential role in tumor development or progression, as it is associated with a specific cancer type (acute myeloid leukaemia). This suggests that the variant may contribute to the oncogenic process in this context.

Oncogenic, Functional evidence:

Oncogenic: The study describes how PIK3CA mutations were assessed for their activity in promoting tumor growth and transformation, indicating that these somatic variants contribute to tumor development or progression.

Functional: The research involved functional assessments of PIK3CA variants through in vitro and in vivo assays, demonstrating that these variants alter molecular activities, such as PI3K signaling and other pathways.

Predictive, Functional evidence:

Predictive: The study discusses the poor response of patients with CRLF2-rearranged acute lymphoblastic leukemia (ALL) to current therapies and suggests that targeting aberrant signaling pathways with JAK inhibitors may improve treatment outcomes, indicating a correlation between the CRLF2 variant and sensitivity to specific therapies.

Functional: The research characterizes the biochemical effects of CRLF2 alterations, demonstrating that TSLP stimulation induces robust signaling through the JAK/STAT and PI3K/mTOR pathways, which indicates that the CRLF2 variant alters molecular signaling functions in these leukemias.

Predictive, Prognostic, Oncogenic evidence:

Prognostic: The study indicates that cytoplasmic cyclin E staining is associated with the greatest risk of recurrence across different breast cancer subtypes, suggesting it correlates with disease outcome independent of therapy.

Predictive: The conclusion mentions that patients with high cytoplasmic cyclin E staining may benefit from alternative therapies targeting the oncogenic isoforms of cyclin E, indicating a correlation with treatment response.

Oncogenic: The abstract refers to targeting the oncogenic isoforms of cyclin E, suggesting that these variants contribute to tumor development or progression.

Predictive, Oncogenic evidence:

Predictive: The study demonstrates that the loss of LKB1 creates vulnerability and renders cells particularly sensitive to ERK inhibitors, indicating a correlation between the LKB1 variant and response to this specific therapy. The findings suggest that LKB1-mutated tumors may benefit from treatment with ERK inhibitors, highlighting the predictive nature of this variant in therapeutic contexts.

Oncogenic: The abstract indicates that LKB1 is one of the most mutated genes in NSCLC and its loss contributes to tumor development and progression, particularly in KRAS-mutated cases. This suggests that the LKB1 variant plays a role in oncogenic processes within these tumors.

Predictive evidence:

Predictive: The overall response rate (ORR) was observed to be greater in patients who were positive for PD-L1 than in those who were negative for PD-L1, indicating that the variant correlates with treatment response to ceritinib plus nivolumab. This suggests that PD-L1 positivity may predict sensitivity to this combination therapy in ALK-rearranged NSCLC patients.

nan evidence:

Missing abstract

Diagnostic, Predisposing evidence:

Diagnostic: The abstract discusses germline mutations in the genes encoding SDH subunits that result in hereditary syndromes associated with various tumors, indicating that these variants are used to classify and define a disease subtype. The mention of "accurate classification of these tumors" further supports their role in diagnosis and genetic evaluation.

Predisposing: The abstract explicitly states that the germline mutations lead to hereditary syndromes, which implies an inherited risk for developing associated tumors. This aligns with the definition of predisposing variants, as they confer risk for disease development through inherited mutations.

Predictive, Oncogenic evidence:

Predictive: The study discusses the efficacy of sorafenib against the imatinib-resistant KITT670I mutation, indicating that this variant correlates with resistance to imatinib and sensitivity to sorafenib, which is a clear example of predictive evidence related to therapy response.

Oncogenic: The mention of the KITT670I mutation in the context of imatinib resistance suggests that this somatic variant contributes to tumor development or progression, as it is associated with a specific cancer type (gastrointestinal stromal tumor) and its resistance mechanisms.

Functional evidence:

Functional: The M13F/R variant is mentioned in the context of PCR primer design, indicating its role in amplifying specific DNA sequences for further analysis. This suggests that the variant is being utilized to alter molecular function in the context of genetic testing.

nan evidence:

Missing abstract

Prognostic evidence:

Prognostic: The study indicates that IKZF1 deletion is associated with inferior 5-year event-free survival (EFS) and higher cumulative incidence of relapse, suggesting that this variant correlates with disease outcome independent of therapy. The multivariable analysis further supports that IKZF1 deletion is an independent predictor of inferior outcome.

Predictive, Prognostic evidence:

Prognostic: The study indicates that fusion-positivity and IKZF1 deletion are associated with inferior event-free survival, suggesting that these genetic alterations correlate with disease outcomes independent of therapy. The mention of a hazard ratio further supports the prognostic significance of these findings.

Predictive: The abstract states that the high-risk B-ALL subtype has demonstrated sensitivity to relevant tyrosine kinase inhibitors, indicating that the presence of kinase-activating fusions correlates with response to specific therapies. This suggests a predictive relationship between the variants and treatment outcomes.

Predictive, Prognostic evidence:

Prognostic: The study reports that patients with IKZF1 gene deletion (IKZF1(del)) had a lower 8-year event-free survival (EFS) of 67.7% compared to 86.5% for those without the deletion, indicating that IKZF1(del) correlates with a poorer disease outcome independent of therapy. The hazard ratio of 2.41 further supports its prognostic significance in B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

Predictive: The results indicate that among IKZF1(del)-positive patients, those receiving vincristine-steroid pulses during maintenance had a significantly higher 8-year EFS of 93.3%, suggesting that IKZF1(del) is predictive of treatment response to this specific therapy. This highlights the variant's role in stratifying patients for more effective treatment options.

Prognostic evidence:

Prognostic: The abstract states that IKZF1 gene deletions are associated with a poor outcome in pediatric precursor B-cell acute lymphoblastic leukemia, specifically noting a lower 5-year event-free survival and a higher cumulative incidence of relapses in patients with these deletions. This indicates that the variant correlates with disease outcome independent of therapy, fulfilling the criteria for prognostic evidence.

Predictive evidence:

Predictive: The G697R mutation is described as conferring high-level resistance to multiple tyrosine kinase inhibitors, indicating its role in predicting treatment response and resistance in patients with FLT3 mutations. This suggests that the presence of the G697R variant may impact the effectiveness of specific therapies, warranting further investigation in clinical settings.

Predictive, Prognostic evidence:

Predictive: The abstract states that "EGFR mutation...correlated with favorable response to TKIs treatment," indicating that this variant is predictive of treatment response. Additionally, it mentions that "KRAS mutation correlated with progressive disease," further supporting its predictive nature regarding resistance to therapy.

Prognostic: The abstract mentions that "PIK3CA mutation correlated with shorter median time to progression (TTP) and worse overall survival (OS)," which indicates that this variant is prognostic for disease outcome independent of therapy. The statement about KRAS mutation correlating with shorter TTP also supports its prognostic significance.

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.

nan evidence:

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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.