Predictive, Diagnostic evidence:

Predictive: The study discusses how patients with acquired MET alterations may derive clinical benefit from therapies that target both ALK and MET, indicating a correlation between the presence of these alterations and response to treatment. This suggests that MET amplification is associated with resistance to ALK inhibitors and that targeting MET can improve treatment outcomes.

Diagnostic: The abstract mentions that MET amplification was detected in 15% of tumor biopsies from patients relapsing on next-generation ALK inhibitors, which indicates that MET alterations can be used to classify or confirm a specific subtype of resistance in ALK-positive lung cancer. This association highlights the role of MET amplification as a biomarker for identifying patients who may experience ALK-independent resistance.

Prognostic evidence:

Prognostic: The study indicates that alterations to the p53 tumor suppressor gene are associated with more aggressive disease in breast cancer, evidenced by shortened survival of patients with mutations. Specifically, mutations within exon 4 and those causing denaturation of the protein structure were linked to poor prognosis, highlighting their impact on overall patient survival.

Prognostic, Functional evidence:

Prognostic: The abstract states that mutations at the Arg248 position are significantly associated with shorter patient survival, indicating a correlation between this variant and disease outcome.

Functional: The abstract mentions that ectopic expression of the p53 mutant R282W significantly upregulated CYP3A4 mRNA and protein levels, demonstrating that this variant alters molecular function related to drug metabolism.

Predictive, Prognostic evidence:

Prognostic: The study reports that TP53 mutations are associated with shorter survival and a shorter time to relapse, indicating that these mutations correlate with disease outcomes independent of therapy. This is supported by the statistical significance (P<0.001) mentioned in the results.

Predictive: The abstract discusses how the presence of RAS pathway mutations and JAK2 mutations correlates with shorter survival and higher risks of relapse and death without relapse, suggesting that these mutations may predict clinical outcomes after allogeneic hematopoietic stem-cell transplantation. The specific mention of these associations with transplantation outcomes supports this classification.

Diagnostic, Prognostic evidence:

Diagnostic: The study assesses the frequency of TP53 alterations in acute myeloid leukemia with complex karyotype (CK-AML) and correlates these alterations with other genetic changes, indicating that TP53 mutations are used to classify and define the disease.

Prognostic: The results indicate that patients with TP53 alterations had significantly lower complete remission rates and inferior overall survival, demonstrating that these alterations 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 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.

Predictive, Prognostic evidence:

Prognostic: The study reports that TP53 mutation is strongly associated with a poor prognosis for overall survival in patients with glioblastoma, indicating that the presence of this variant correlates with disease outcome independent of therapy.

Predictive: The findings suggest that mutant TP53 decreases the chemosensitivity of glioblastoma to temozolomide, indicating a correlation between the variant and resistance to this specific therapy.

Prognostic, Oncogenic evidence:

Oncogenic: The study indicates that mutations in the ARID2 gene are commonly found in hepatocellular carcinoma (HCC) and that ARID2 plays a significant role in cancer development, particularly in relation to metastasis. The evidence of ARID2 knockout promoting pulmonary metastasis in HCC mouse models supports the notion that ARID2 mutations contribute to tumor progression.

Prognostic: The abstract mentions a positive association between ARID2 expression and survival of HCC patients, indicating that lower levels of ARID2 correlate with poorer outcomes. This suggests that ARID2 may serve as a prognostic marker for HCC, as its expression levels are linked to disease progression and patient survival.

Prognostic evidence:

Prognostic: The abstract states that YAP1 is an important prognostic biomarker for pancreatic cancer, indicating a correlation with disease outcome independent of therapy. This suggests that the presence of the variant may be associated with survival or progression in patients with pancreatic cancer.

Predictive, Diagnostic, Prognostic evidence:

Predictive: The study indicates that high APOBEC3B expression is associated with improved progression-free survival and sensitivity to cisplatin and carboplatin, suggesting that it may serve as a predictive biomarker for therapeutic response to platinum-based chemotherapy.

Prognostic: The results show that high APOBEC3B expression correlates with improved progression-free survival and moderately with overall survival, indicating its potential role as a prognostic factor independent of therapy.

Diagnostic: The study identifies APOBEC3B as a candidate biomarker for detection and intervention in clear cell ovarian carcinoma, suggesting its use in classifying or confirming the disease.

Predictive, Prognostic evidence:

Prognostic: The abstract states that "IL-6 was significantly associated with poor prognosis in patients with esophageal cancer," indicating that the variant correlates with disease outcome independent of therapy.

Predictive: The mention of "treatment resistance" in the context of targeting IL-6 suggests that this variant may correlate with resistance to specific therapies, indicating its predictive value for treatment response.

Predictive, Prognostic evidence:

Predictive: The study found that preoperative plasma levels of IL-6 and IL-6sR were independent predictors of lymphovascular invasion, metastases to lymph nodes, disease recurrence, and disease-specific survival, indicating their potential role in predicting treatment outcomes.

Prognostic: The results indicated that high levels of IL-6 and IL-6sR predicted disease-specific survival, demonstrating their correlation with disease outcomes independent of therapy.

Prognostic evidence:

Prognostic: The study identifies high levels of serum IL-6 as an independent adverse prognostic variable for overall survival in patients with hormone-refractory metastatic breast cancer, indicating a correlation between IL-6 levels and poor survival outcomes.

Prognostic, Oncogenic evidence:

Prognostic: The study indicates that low BAP1 mRNA levels are associated with overall survival (OS) in cutaneous melanoma (CM) patients, with specific hazard ratios provided (HR = 0.73), suggesting a correlation between the variant and disease outcome independent of therapy.

Oncogenic: The presence of BAP1 point mutations, including E30K and P30, is discussed in the context of their unknown significance in tumors, indicating that these somatic variants may contribute to tumor development or progression, although they were not associated with overall survival in CM.

Predictive, Prognostic evidence:

Prognostic: The abstract states that "all three genes were associated with a poor prognosis in human patients," indicating that the variants correlate with disease outcome independent of therapy. This suggests that the presence of these proteins is linked to survival rates in patients with pancreatic ductal adenocarcinoma (PDAC).

Predictive: The abstract mentions that "precise interventions targeting cancer cell-derived matrisome proteins, such as AGRN, SERPINB5, and CSTB, may represent preferred potential therapeutic targets," which implies that these variants could influence treatment response or resistance, thus providing predictive evidence regarding their role in therapy.

nan evidence:

Missing abstract

Prognostic evidence:

Prognostic: The study reports that glioma patients with higher expression of KIF3C had longer survival time, indicating a correlation between KIF3C expression and disease outcome independent of therapy. This is further supported by subgroup analysis showing that higher KIF3C expression predicted longer survival time in the low-grade glioma group.

Predictive, Oncogenic evidence:

Predictive: The study discusses how ATRX mutations lead to increased sensitivity to the WEE1 inhibitor AZD1775, indicating a correlation between the ATRX variant and response to this specific therapy. This suggests that targeting WEE1 could be a therapeutic strategy for ATRX-deficient cancers, highlighting the predictive nature of the variant in relation to treatment response.

Oncogenic: The abstract mentions that ATRX is frequently mutated in tumors, including gliomas and liver cancers, and that these mutations contribute to tumor growth and survival, which aligns with the definition of oncogenic variants that drive tumor development or progression. The identification of ATRX mutations as a target for therapeutic intervention further supports its role in oncogenesis.

Predictive, Prognostic, Oncogenic evidence:

Prognostic: The abstract states that "Low levels of ARID1A were associated with a poor prognosis," indicating that the variant correlates with disease outcome independent of therapy.

Oncogenic: The abstract mentions that "Depletion of ARID1A activated an oncogenic transcriptome that drove SCC progression," suggesting that the variant contributes to tumor development or progression.

Predictive: The abstract discusses the potential of parthenolide as a treatment for patients with low ARID1A expression, indicating that the variant's status may correlate with response to this specific therapy.

Predictive, Oncogenic evidence:

Predictive: The study discusses the use of KRASG12C inhibitors and their effects on signaling and viability, indicating a correlation with treatment response and resistance mechanisms. The mention of "adaptive feedback" and "enhance efficacy" suggests that the variant's presence influences the effectiveness of specific therapies targeting KRASG12C.

Oncogenic: The abstract describes KRAS as the most commonly mutated oncogene and discusses the KRASG12C mutation in the context of tumor development and progression, indicating that this somatic variant contributes to cancer biology. The focus on the KRASG12C mutation and its role in signaling pathways further supports its classification as oncogenic.

Oncogenic, Functional evidence:

Oncogenic: The study describes a partial duplication of the switch 2 domain of K-Ras in a patient with juvenile myelomonocytic leukaemia, indicating that this somatic variant contributes to tumor development or progression, as it is associated with a myeloproliferative neoplasm characterized by driver Ras pathway mutations.

Functional: The variant is shown to result in a protein with altered electrophoretic mobility, suggesting that the duplication affects the molecular function of K-Ras, specifically its conformation and possibly its interaction with other proteins, as indicated by the immunoblot analysis.

Predictive, Prognostic, Oncogenic evidence:

Prognostic: The study indicates that KRAS mutation is significantly associated with worse overall survival (OS) and disease-free survival (DFS) in early stage resected NSCLC, suggesting that the presence of this mutation correlates with poorer disease outcomes.

Predictive: The findings also show that KRAS mutation is associated with inferior outcomes of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) treatment and chemotherapy, indicating that this variant may predict resistance to these therapies.

Oncogenic: The paper discusses KRAS as the most frequently mutated oncogene in NSCLC, which implies that mutations in this gene contribute to tumor development and progression, supporting its classification as an oncogenic variant.

Oncogenic, Functional evidence:

Oncogenic: The study investigates the effect of the C118S mutation on tumorigenesis, demonstrating that KrasC118S alleles impede urethane-induced lung tumorigenesis, indicating that this somatic variant contributes to tumor development.

Functional: The abstract discusses how the thiol residue of cysteine 118 (C118) is crucial for the activation of Ras proteins through redox-dependent reactions, suggesting that the C118S mutation alters the molecular function of Ras, impacting its activation and subsequent signaling pathways.

Predictive, Oncogenic evidence:

Predictive: The study discusses how the BRAF V600E mutation correlates with treatment response, specifically noting that combination therapy with BRAF and multitargeting TK inhibitors may be more effective than single-agent therapies, indicating a predictive relationship between the variant and therapy response.

Oncogenic: The BRAF V600E mutation is implicated in tumor development and progression, as evidenced by the significant inhibition of proliferation, colony formation, invasion, and migration in BRAF V600E thyroid cancer cell lines, demonstrating its role as a somatic variant contributing to cancer behavior.

Predictive, Diagnostic evidence:

Predictive: The study demonstrates that the addition of panitumumab to chemotherapy significantly improves progression-free survival (PFS) in patients with wild-type (WT) KRAS tumors, indicating that KRAS status is predictive of treatment response to panitumumab. The results show a clear correlation between the presence of WT KRAS and improved outcomes with the therapy, highlighting the variant's role in determining sensitivity to treatment.

Diagnostic: The study uses KRAS status to classify patients into wild-type and mutant categories, which is essential for determining eligibility for panitumumab treatment. This classification is indicative of the variant's role in defining a specific disease subtype (mCRC with WT KRAS), thus supporting its use as a diagnostic marker.

Predictive, Prognostic evidence:

Prognostic: The abstract states that the KRAS mutation had an adverse impact on the prognosis for stage IV CRC patients, indicating that the presence of this mutation correlates with disease outcome independent of therapy.

Predictive: The results section discusses the mutation status of the KRAS gene as a predictive marker for the response to anti-EGFR antibody therapies in patients with metastatic colorectal cancer, suggesting that specific mutations, including G13D, are associated with sensitivity or resistance to treatment.

Functional evidence:

Functional: The study provides evidence that specific mutations in the rasH gene alter molecular function, particularly in terms of GTPase activity and guanine nucleotide exchange rates. For instance, the mutation Val-146 resulted in a significant increase in nucleotide exchange, which is directly linked to its transforming potential, demonstrating a clear alteration in biochemical function.

Oncogenic, Functional evidence:

Oncogenic: The study discusses the role of activated Kras2 mutations in the development of lung tumors, indicating that these mutations contribute to tumor progression, particularly in the context of loss of the wildtype Kras2 allele. The evidence of activating Kras2 mutations in all chemically induced lung tumors supports the classification of this variant as oncogenic.

Functional: The abstract mentions that wildtype Kras2 inhibits colony formation and tumor development in transformed cells, suggesting that it alters molecular function related to tumor suppression. This indicates that the variant has a functional role in regulating cellular processes associated with tumorigenesis.

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Predictive, Diagnostic, Oncogenic evidence:

Diagnostic: The study examines the association of KIT and PDGFRA mutations with clinicopathological factors in gastrointestinal stromal tumors (GIST), indicating that these mutations can be used to classify or define the disease and its subtypes.

Predictive: The conclusion states that the determination of KIT and PDGFRA mutations should be additional parameters for better prediction of GISTs clinical behavior, suggesting a correlation with treatment response or disease progression.

Oncogenic: The presence of specific mutations in the KIT gene, particularly the deletion/insertion mutations affecting codons 557/558, is associated with potentially malignant clinical behavior, indicating that these somatic variants contribute to tumor development or progression.

Predictive evidence:

Predictive: The study assesses the dose dependency of response and progression-free survival with imatinib for metastatic GIST, indicating that the variant correlates with treatment response and sensitivity to the therapy. The findings show a significant difference in progression-free survival between the two dosing regimens, which supports the predictive nature of the variant in relation to therapy outcomes.

Predictive, Oncogenic evidence:

Predictive: The study identifies high levels of Trop2 as predictive of recurrence in localized prostate cancer and suggests that these levels could indicate sensitivity to Trop2-targeting therapies and PARP1 inhibition, highlighting the variant's role in treatment response.

Oncogenic: The findings indicate that Trop2 drives prostate cancer growth and induces a neuroendocrine phenotype, demonstrating its contribution to tumor development and progression, which is characteristic of oncogenic behavior.

Predictive, Diagnostic evidence:

Predictive: The study discusses the activity of afatinib in patients with tumors harboring uncommon EGFR mutations, including T790M, and evaluates key endpoints such as overall response rate and time to treatment failure, indicating a correlation with treatment response.

Diagnostic: The variant T790M is categorized among uncommon EGFR mutations, suggesting its role in defining the subtype of NSCLC and its association with specific treatment responses.

Predictive evidence:

Predictive: The study discusses that patients with BRAF V600 mutation-positive pLGG may benefit from treatment with dabrafenib, indicating a correlation between the BRAF V600 mutation and response to this specific therapy. The mention of objective response rates (ORRs) further supports the predictive nature of the variant in relation to treatment outcomes.

Diagnostic, Prognostic evidence:

Prognostic: The study indicates that ATRX alterations are associated with a significantly improved overall survival (OS) rate in glioma patients, suggesting that these mutations correlate with disease outcome independent of therapy.

Diagnostic: The authors mention that ATRX mutations have clinical implications for the molecular diagnosis of gliomas, indicating that these mutations can provide diagnostic information for classifying or confirming the disease.

Diagnostic, Prognostic evidence:

Prognostic: The study indicates that patients who are PAX3/FOXO1 positive have a significantly poorer outcome compared to other groups, suggesting that this variant correlates with disease outcome independent of therapy. The mention of "significantly poorer outcome" directly supports its classification as prognostic evidence.

Diagnostic: The abstract discusses the incorporation of the PAX3/FOXO1 fusion gene status into a risk-stratification scheme, which implies that this variant is used to classify or define a subtype of rhabdomyosarcoma. The use of the term "fusion gene status" indicates its role in diagnosis and classification of the disease.

Predictive evidence:

Predictive: The study identifies EGFR amplification as a potential biomarker to predict sensitivity to PARP inhibition, indicating that this variant correlates with the response to talazoparib treatment in glioblastoma patients. The results demonstrate that EGFR-amplified glioma sphere-forming cells showed remarkable sensitivity to talazoparib, supporting the predictive nature of this variant in therapy selection.

Predisposing evidence:

Predisposing: The study discusses familial cases of rhabdoid tumors linked to heterozygous SMARCB1 germline mutations, indicating that these mutations confer inherited risk for developing the disease. Additionally, the identification of a germline mutation in SMARCA4 in two sisters with rhabdoid tumors further supports the notion of inherited predisposition to this cancer type.

Diagnostic, Prognostic, Oncogenic evidence:

Diagnostic: The study discusses BCOR-CCNB3 sarcoma (BCS) as a recently defined genetic entity among undifferentiated round cell sarcomas, indicating that it is classified based on its genetic alterations, such as BCOR internal tandem duplication (ITD) and BCOR-MAML3. This classification suggests that the presence of these variants is used to define and confirm the disease subtype.

Prognostic: The follow-up data indicates a 5-year overall survival rate of 72% for patients with BCS, which is reported independently of any specific therapy context. This suggests that the variant correlates with disease outcome, making it prognostic in nature.

Oncogenic: The abstract mentions that BCS shows consistent BCOR overexpression and that the morphologic features and immunoprofile overlap with other tumors exhibiting BCOR oncogenic upregulation. This indicates that the BCOR genetic alterations contribute to tumor development or progression, classifying it as oncogenic.

Diagnostic, Oncogenic evidence:

Diagnostic: The study identifies a new fusion between BCOR and CCNB3 as a powerful diagnostic marker for a specific subgroup of sarcoma, indicating its role in classifying and defining this disease subtype.

Oncogenic: The presence of the BCOR-CCNB3 fusion is described as contributing to tumor development, as it activates S phase in NIH3T3 cells, demonstrating its role in oncogenesis.

Diagnostic, Oncogenic evidence:

Diagnostic: The study discusses the BCOR-CCNB3 fusion gene as a marker for genetic subclassification of undifferentiated unclassified sarcomas, indicating its potential use in reproducible diagnosis. The identification of this fusion in multiple cases supports its role in defining a specific subtype of sarcoma.

Oncogenic: The presence of the BCOR-CCNB3 fusion gene in undifferentiated spindle cell sarcomas suggests that it contributes to tumor development, as indicated by its identification in multiple tumor samples and the context of its association with a specific cancer type.

Oncogenic evidence:

Oncogenic: The study discusses the EWS-WT1 chimaeric protein resulting from the t(11;22)(p13;q12) translocation, indicating that this fusion contributes to tumor development by inducing the expression of PDGFA, which is associated with the reactive fibrosis characteristic of desmoplastic small round-cell tumor (DSRT). This suggests that the EWS-WT1 fusion plays a role in the oncogenic process of this specific malignancy.

Oncogenic evidence:

Oncogenic: The study discusses the EWS-WT1 chimeric protein resulting from the t(11;22)(p13;q12) translocation, indicating that this somatic variant contributes to the malignant phenotype of desmoplastic small round cell tumor (DSRCT) and is involved in tumor development and progression. The mention of the dysregulated expression of EWS-WT1 targets further supports its role in oncogenesis.

Diagnostic, Oncogenic evidence:

Diagnostic: The abstract states that "immunohistochemical testing for the SMARCB1/INI1 antibody has been considered useful in confirming the histologic diagnosis of malignant rhabdoid tumors," indicating that the variant is used to define or confirm a specific disease subtype.

Oncogenic: The abstract describes SMARCB1/INI1 as a "potent and bona fide tumor suppressor" and discusses its interactions with pathways related to tumor proliferation and progression, suggesting that alterations in this gene contribute to tumor development or progression.

Oncogenic evidence:

Oncogenic: The study provides evidence that biallelic inactivating mutations of the hSNF5 gene are associated with malignant rhabdoid tumors (MRT), indicating that Snf5 functions as a tumor suppressor and contributes to tumor development, particularly in the context of the observed tumors in heterozygous mice.

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 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.