Predictive, Diagnostic evidence:

Predictive: The study discusses how multiple clinical-grade antiandrogens slowed the growth of and radiosensitized AR-positive GBM cell lines and patient-derived xenografts (PDXs), indicating a correlation between the androgen receptor (AR) expression and response to therapy. This suggests that AR expression may predict sensitivity to antiandrogen treatment in glioblastoma.

Diagnostic: The abstract mentions that nearly half of GBM cell lines, PDXs, and human tumors expressed AR, indicating that AR expression can be used to classify or define a subtype of glioblastoma, specifically AR-positive GBMs. This association with a specific characteristic of the tumors supports its use as a diagnostic marker.

Prognostic evidence:

Prognostic: The study indicates that increasing CtBP2 expression in lung adenocarcinoma (LUAD) is significantly correlated with patients' survival, suggesting that it serves as a prognostic marker for the disease. The Kaplan-Meier survival analyses performed in the study further support this correlation with specific statistical significance (P = .028).

Predictive, Diagnostic evidence:

Diagnostic: The abstract discusses the molecular profiling efforts that have advanced the understanding of biologically and clinically heterogeneous disease subgroups in medulloblastoma, indicating that these efforts are aimed at improving diagnostic interventions.

Predictive: The mention of "translational opportunities" and "improved diagnostic and therapeutic interventions" suggests that the insights gained from molecular characterization may correlate with response to therapies, indicating a predictive aspect of the variant in relation to treatment outcomes.

Predictive evidence:

Predictive: The abstract discusses brigatinib as an ALK inhibitor with superior efficacy and tolerability, indicating its potential as a first-line treatment for ALK-positive NSCLC, which suggests a correlation between the ALK variant and response to this therapy.

nan evidence:

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Predictive, Prognostic evidence:

Predictive: The study reports that alectinib significantly improved progression-free survival (PFS) compared to crizotinib in treatment-naive ALK-positive non-small-cell lung cancer (NSCLC), indicating a correlation between the variant and response to therapy. The mention of "significantly prolonged investigator-assessed PFS" supports the predictive nature of the variant in relation to treatment outcomes.

Prognostic: The abstract discusses overall survival (OS) data, noting that the 5-year OS rate was higher with alectinib compared to crizotinib, which suggests that the variant correlates with disease outcome independent of therapy. The mention of "median OS was not reached with alectinib" further emphasizes the prognostic implications of the variant in this context.

Predictive, Diagnostic evidence:

Predictive: The study discusses the antitumor activity of a DRD1 agonist in combination with temozolomide (TMZ), indicating that DRD1 activation correlates with a therapeutic response in glioblastoma (GBM) cells. The mention of a "synergistic therapeutic effect" suggests that the variant's role is predictive of treatment outcomes.

Diagnostic: The expression of DRD1 in human GBM tissues is associated with a good clinical outcome, which implies that it may be used to classify or define a subtype of GBM based on its expression levels. This association supports the use of DRD1 as a potential biomarker in diagnosing or characterizing GBM.

Predictive, Functional evidence:

Predictive: The study discusses the role of miR-320a in relation to cisplatin resistance in lung adenocarcinoma, indicating that the expression levels of this miRNA correlate with treatment response, specifically in the context of chemotherapy. The mention of "cisplatin resistance" directly relates to the predictive nature of the variant's impact on therapy response.

Functional: The study investigates the biological function of miR-320a and its target genes, suggesting that it alters molecular functions related to tumor progression and signaling pathways. This aligns with the functional evidence type as it focuses on the molecular and biochemical roles of the miRNA.

Diagnostic evidence:

Diagnostic: The study discusses the development of a tool for discovering disease-related biomarkers, which implies that the variants are being used to classify or define a disease at the miRNA-set level. This aligns with the definition of diagnostic evidence as it relates to identifying disease associations.

Predictive, Prognostic evidence:

Predictive: The study indicates that higher baseline levels of OPN, VCAM-1, and PDGF-AA may predict progression-free survival (PFS) benefit from regorafenib compared with placebo, suggesting a correlation between these biomarkers and treatment response. Additionally, VCAM-1 was identified as potentially predictive of overall survival (OS) benefit from regorafenib, further supporting its role in therapy response.

Prognostic: The results highlight that six markers were found to be prognostic for progression-free survival (PFS) and nine markers for overall survival (OS), indicating that these biomarkers correlate with disease outcomes independent of therapy. This suggests their potential utility in assessing prognosis for patients with metastatic colorectal cancer.

Diagnostic, Prognostic evidence:

Diagnostic: The abstract states that SPC25 is an "effective diagnostic and prognostic biomarker for HCC," indicating its role in classifying or confirming the disease.

Prognostic: The abstract mentions that SPC25 "independently predicted poor overall survival of patients with HCC," which correlates the variant with disease outcome independent of therapy.

Prognostic, Oncogenic evidence:

Prognostic: The abstract indicates that patients with cholangiocarcinoma (CCA) harboring mutant IDH1 have a better prognosis than those with wild-type IDH1, suggesting a correlation between the IDH1 mutation status and disease outcome. This aligns with the definition of prognostic evidence, as it discusses survival outcomes independent of therapy.

Oncogenic: The study discusses the role of TET1 in CCA progression, indicating that TET1 contributes to tumor development and malignancy in CCA cells. This suggests that TET1 is involved in oncogenic processes, supporting its classification as an oncogenic variant.

Diagnostic evidence:

Diagnostic: The abstract discusses the identification of a mutation in GNAQ (c.626A>c, p.Gln209Pro) in a patient with congenital hemangioma, indicating that this variant is used to classify and confirm the diagnosis of the vascular tumor. The mention of "utility of targeted genetic testing to elucidate the exact mutation and thus classification of vascular tumors" further supports its role in diagnosis.

Predictive evidence:

Predictive: The study discusses how loss of Man2a1 in cancer cells increases their sensitivity to T-cell-mediated killing and enhances response to anti-PD-L1 treatment, indicating a correlation with treatment response. Additionally, the mention of swainsonine synergizing with anti-PD-L1 treatment further supports the predictive nature of the variant in relation to therapy efficacy.

Predictive, Oncogenic evidence:

Predictive: The study identifies that FGFR/FGF alterations lead to resistance to ER-directed therapies, specifically fulvestrant, indicating a correlation with treatment response. The mention of reversing resistance with FGFR inhibitors and other targeted therapies further supports the predictive nature of these findings regarding therapy sensitivity.

Oncogenic: The alterations in the FGFR pathway, including FGFR1, FGFR2, and FGF3 amplifications or mutations, are described as contributing to the development of resistance in ER+ breast cancer, suggesting a role in tumor progression. The evidence of these alterations being enriched under selective pressure from ER-directed therapy indicates their oncogenic potential.

Predictive, Diagnostic evidence:

Predictive: The study discusses how high levels of ERBB2 mRNA are associated with better response and progression-free survival in patients treated with T-DM1, indicating that ERBB2 expression correlates with treatment response. This suggests that ERBB2 levels can be used to predict the efficacy of T-DM1 therapy in HER2-positive metastatic breast cancer.

Diagnostic: The abstract mentions that the study analyzed ERBB2 expression in various tumor samples and identified a subset of tumors as ERBB2-high, which implies that ERBB2 levels can be used to classify or define a specific subtype of breast cancer and potentially other cancer types. This classification supports the use of ERBB2 as a biomarker in clinical settings.

Diagnostic, Predisposing evidence:

Diagnostic: The study mentions that polymorphic variants in LUZP2, including rs7943454, are associated with late-onset Alzheimer's disease, indicating its role in defining or classifying a disease.

Predisposing: The association of rs7943454 with the onset risk of Alzheimer's disease suggests that this variant may confer inherited risk for developing the disease, which aligns with the definition of a predisposing variant.

Predictive, Diagnostic evidence:

Diagnostic: The variant BRCA1:c.185delAG is mentioned as a pathogenic mutation represented by multiple patients in the dataset, indicating its role in defining or classifying a disease subtype. This suggests that the variant is used to confirm the presence of a specific genetic alteration associated with the disease.

Predictive: The abstract discusses reversion mutations in BRCA1 or BRCA2 being associated with resistance to PARP inhibitors and platinum, which implies that the presence of certain mutations, including BRCA1:c.185delAG, may correlate with treatment response or resistance. This indicates a predictive relationship between the variant and therapeutic outcomes.

Predictive, Diagnostic, Prognostic evidence:

Diagnostic: The study identifies SMARCA4 mutations as common alterations in non-small cell lung cancer (NSCLC) and discusses their association with other genomic abnormalities, indicating their role in classifying the disease.

Prognostic: The results indicate that SMARCA4 alterations are associated with shorter overall survival in patients with metastatic NSCLC, highlighting their significance as independent predictors of poor prognosis.

Predictive: The study reports that treatment with immune checkpoint inhibitors (ICI) is associated with improved outcomes in patients with SMARCA4-mutant tumors, suggesting that these mutations may correlate with sensitivity to this specific therapy.

Diagnostic, Functional evidence:

Diagnostic: The study identifies the TP53 c.1000G>C;p.G334R variant as a mutation associated with Li-Fraumeni syndrome (LFS), indicating its role in defining and confirming this familial cancer syndrome. The mention of the variant being found predominantly in Ashkenazi Jewish individuals further supports its diagnostic relevance in this population.

Functional: The transient transfection of the p.G334R allele demonstrated a mild defect in colony suppression assays, indicating that this variant alters the molecular function of the p53 protein. Additionally, the study reports that the G334R-mutant protein shows thermal instability and defective transactivation of certain p53 target genes, further supporting its functional impact.

Oncogenic, Functional evidence:

Oncogenic: The abstract discusses how IL6/STAT3 signaling drives metastasis in ER+ breast cancer, indicating that this pathway contributes to tumor development and progression, which aligns with the definition of an oncogenic variant.

Functional: The study highlights that STAT3 hijacks a subset of ER enhancers to drive a distinct transcriptional program, suggesting that the variant alters molecular function, specifically in the context of transcriptional regulation.

Predictive, Oncogenic evidence:

Predictive: The study discusses how blockade of the NRG1/HER3 axis can re-sensitize prostate cancer models to antiandrogen therapy, indicating that the variant may correlate with resistance to this specific therapy.

Oncogenic: The evidence suggests that the cancer-associated fibroblasts and their secretion of NRG1 contribute to tumor progression by activating HER3 signaling in prostate cancer cells, which aligns with the definition of a somatic variant contributing to tumor development.

Predictive, Oncogenic evidence:

Oncogenic: The study discusses a MYC-miRNA-MXI1 feedback loop that regulates proliferation and tumorigenesis in glioma, indicating that the variant contributes to tumor development or progression.

Predictive: The abstract mentions that the ethyl ester form of meclofenamic acid (MA2) enhances the effect of the chemotherapy drug temozolomide on suppressing proliferation of glioma cells, suggesting a correlation between the variant and response to therapy.

Functional evidence:

Functional: The abstract indicates that miR-146a and miR-26a could counteract biological effects of CEACAM6, suggesting that these variants alter molecular or biochemical functions related to CEACAM6. This implies a role in modulating the activity or expression of this gene, which aligns with the definition of functional evidence.

Prognostic evidence:

Prognostic: The study indicates that elevated SERINC2 expression predicted shorter overall survival (OS) in low-grade glioma (LGG) patients, suggesting that SERINC2 expression may serve as a prognostic marker for this patient group. The Cox regression analysis further supports that SERINC2 is an independent factor in determining OS for LGG patients.

Predisposing evidence:

Predisposing: The abstract discusses an "inherited contribution to primary brain cancer" and mentions the identification of "candidate predisposition genes," indicating that the variant rs3198697 is associated with inherited risk for developing brain cancer. The context of linkage analysis in high-risk pedigrees further supports this classification.

Predictive, Prognostic evidence:

Prognostic: The study reports on overall survival (OS) in patients with EGFR-mutated NSCLC and leptomeningeal metastases, indicating that T790M mutational status does not significantly affect median OS (10.1 months vs. 9.0 months, p = 0.936). This suggests that the T790M variant's presence does not correlate with disease outcome in this context, which aligns with the definition of prognostic evidence.

Predictive: The abstract discusses the treatment response to osimertinib in patients with T790M mutational status, indicating that patients treated with osimertinib had a superior OS compared to those not treated, regardless of T790M status. This suggests that the T790M variant may not predict response to osimertinib, but the context of treatment response is still relevant, thus supporting the predictive classification.

Predictive, Oncogenic evidence:

Predictive: The study discusses how the combination of DNMTi guadecitabine and PARPi talazoparib enhances the efficacy of PARPi therapy, indicating a correlation with treatment response irrespective of BRCA mutation status. This suggests that the variant's presence or absence does not affect the sensitivity to the combined therapy, which is a predictive aspect of the variant's role in treatment outcomes.

Oncogenic: The results indicate that the combination treatment decreased xenograft tumor growth, which implies that the variant contributes to tumor development or progression in the context of breast and ovarian cancers. This aligns with the oncogenic evidence type as it demonstrates the variant's role in cancer biology.

Prognostic evidence:

Prognostic: The abstract states that "Overexpressed SNHG6 was significantly associated with poor prognosis in various cancers," indicating that the variant correlates with disease outcome independent of therapy. This suggests that SNHG6 levels can be used to evaluate prognosis in cancer patients.

Prognostic evidence:

Prognostic: The study indicates that high LPAR1 expression is correlated with favorable overall survival in prostate cancer, suggesting its role as a prognostic biomarker. This correlation with survival outcomes, independent of therapy, supports the classification as prognostic evidence.

Oncogenic evidence:

Oncogenic: The abstract states that the mutant protein FOXL2C134W is considered to be a driver of oncogenesis in adult-type ovarian granulosa cell tumors (AGCT), indicating that this somatic variant contributes to tumor development. Additionally, the study describes how FOXL2C134W interacts with SMAD4 to influence gene expression related to tumorigenesis, further supporting its role in cancer progression.

Diagnostic, Oncogenic, Functional evidence:

Diagnostic: The abstract states that the somatic missense point mutation c.402C>G (p.C134W) in the FOXL2 transcription factor is "pathognomonic for adult-type granulosa cell tumors (AGCT) and a diagnostic marker for this tumor type," indicating its role in defining and classifying the disease.

Oncogenic: The abstract mentions that FOXL2C134W "drives AGCT by altering the binding affinity of FOXL2-containing complexes to engage an oncogenic transcriptional program," suggesting that this variant contributes to tumor development or progression.

Functional: The study describes how FOXL2C134W is associated with "altered DNA-binding specificity," indicating that the variant affects molecular function, specifically the binding activity of the FOXL2 protein.

Prognostic evidence:

Prognostic: The study indicates that high expression of MMP14 correlates with a poor short-term prognosis in muscle-invasive bladder cancer (MIBC), as evidenced by survival analyses conducted with clinical follow-up data. This suggests that MMP14 expression is a significant factor in determining disease outcome independent of therapy.

Prognostic, Functional evidence:

Prognostic: The study found that the expression level of LINC00460 was significantly upregulated in NSCLC tissues and cell lines, and particularly negatively correlated with overall survival (OS), indicating its potential as a prognostic marker for disease outcome.

Functional: The results demonstrated that LINC00460 knockdown inhibited the proliferation of A549 cells and promoted their apoptosis, suggesting that LINC00460 alters the molecular function related to cell growth and survival.

Oncogenic evidence:

Oncogenic: The gain-of-function mutation E76K in SHP2 promotes CAC tumorigenesis and induces EMT via the Wnt/beta-catenin signaling pathway, indicating that this variant contributes to tumor development and progression.

Diagnostic, Prognostic, Functional evidence:

Diagnostic: The study identifies TNNT2 as significantly upregulated in colorectal cancer (CRC) samples compared to adjacent normal samples, indicating its potential use as a biomarker for CRC.

Prognostic: Increased expression of TNNT2 was associated with inferior prognosis in both the TCGA training dataset and the GSE17531 validation dataset, suggesting that it correlates with disease outcome.

Functional: The study conducted functional enrichment analysis revealing that the ErbB signaling pathway and glycerophospholipid metabolism pathway were significantly activated in the TNNT2 high expression group, indicating that TNNT2 alters molecular functions related to these pathways.

Predictive, Prognostic evidence:

Predictive: The study discusses the addition of trastuzumab (T) to carboplatin/paclitaxel (C/P) and its impact on progression-free survival (PFS) and overall survival (OS) in patients with HER2/Neu-positive uterine-serous-carcinoma (USC). The results indicate that the combination therapy significantly improves PFS and OS, demonstrating a predictive relationship between the HER2/Neu-positive variant and treatment response.

Prognostic: The results show that the median overall survival (OS) was higher in the trastuzumab arm compared to the control arm, indicating that the HER2/Neu-positive status correlates with better survival outcomes independent of therapy. This suggests a prognostic role of the variant in determining disease outcome.

Predictive, Prognostic evidence:

Prognostic: The abstract states that "PDCD1 upregulation was found in more malignant phenotypes of glioma and indicated a worse prognosis," indicating a correlation between the variant and disease outcome independent of therapy.

Predictive: The mention of "Immunotherapy of targeting PD-1 or combined with other checkpoint molecules... may represent a promising treatment strategy for glioma" suggests that the variant is associated with response to specific therapies, indicating its predictive nature.

Functional evidence:

Functional: The study demonstrates that BRCA1 variants of uncertain significance (VUS) were tested for their ability to complement Brca1-deficient mouse embryonic stem cells in homologous recombination DNA repair (HRR), indicating that these variants alter molecular function related to DNA repair mechanisms. The results showed that 45 out of 238 VUS exhibited functional defects, confirming the impact of these variants on HRR.

Predictive, Prognostic evidence:

Predictive: The study demonstrates that the presence of ESR1 mutations correlates with progression-free survival (PFS) and overall survival (OS) in patients treated with exemestane and fulvestrant, indicating that these mutations can predict treatment response. The interaction between ESR1 mutation status and treatment outcomes further supports this predictive relationship.

Prognostic: The results indicate that patients with detected ESR1 mutations have inferior PFS and OS, suggesting that these mutations are associated with worse disease outcomes independent of the specific therapy used. This correlation highlights the prognostic significance of ESR1 mutations in hormone receptor-positive metastatic breast cancer.

Predictive, Oncogenic evidence:

Predictive: The study indicates that neuroblastoma cell lines harboring the NRAS Q61K mutation were resistant to SHP2 inhibitors, suggesting a correlation between the presence of this variant and resistance to specific therapies. This highlights the predictive nature of the variant in terms of treatment response.

Oncogenic: The mention of the NRAS Q61K mutation being commonly detected at relapse implies its role in tumor development or progression, supporting the classification of this variant as oncogenic. The context of resistance to therapies further emphasizes its contribution to cancer behavior.

Oncogenic evidence:

Oncogenic: The abstract indicates that HSP47 supports the growth of colorectal cancer (CRC) tumors, suggesting that this variant contributes to tumor development or progression. The mention of its role in modulating AKT signaling further supports its oncogenic potential.

Predictive, Oncogenic evidence:

Predictive: The abstract mentions that taletrectinib has potent preclinical activity against the ROS1 G2032R solvent-front mutation, indicating that this variant correlates with response to the therapy. The context of discussing treatment efficacy suggests a predictive relationship between the variant and therapeutic response.

Oncogenic: The mention of the ROS1 G2032R mutation in the context of being a target for a tyrosine kinase inhibitor implies that this somatic variant contributes to tumor development or progression, which aligns with the oncogenic evidence type.

Prognostic evidence:

Prognostic: The abstract states that "High expression level of UPP1 predicts poor prognosis in glioma," indicating that the variant correlates with disease outcome independent of therapy.

Oncogenic evidence:

Oncogenic: The study indicates that the BRAF mutation p.K601E is shown to be oncogenic and can be targeted by MEK inhibitors, suggesting its role in tumor development or progression in chronic lymphocytic leukemia (CLL).

Predictive, Functional evidence:

Predictive: The presence of the BCL-2 G101V mutation in patient samples was predictive of clinical progression, indicating that this variant correlates with resistance to venetoclax therapy in chronic lymphocytic leukaemia patients.

Functional: The BCL-2 G101V mutation reduces the affinity for venetoclax by approximately 180-fold while maintaining affinity for pro-apoptotic proteins, demonstrating that this variant alters the molecular function of the BCL-2 protein in the context of drug interaction.

Predictive, Oncogenic evidence:

Predictive: The study discusses the resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in the context of the T790M mutation, indicating that this variant is associated with resistance to therapy, which is a key aspect of predictive evidence.

Oncogenic: The mention of T790M in relation to EGFR-TKI resistance suggests that this somatic variant contributes to tumor progression and development, aligning with the definition of oncogenic evidence.

Oncogenic evidence:

Oncogenic: The variant EGFR G724S is described as an acquired mutation in patients who developed resistance to osimertinib, indicating its role in tumor progression and resistance mechanisms. This suggests that G724S contributes to the oncogenic process in the context of EGFR-mutant lung cancers.

Predictive, Oncogenic evidence:

Oncogenic: The TP53 Y220C missense mutation is described as a "deleterious somatic mutation," indicating its role in tumor development or progression, which aligns with the definition of oncogenic evidence.

Predictive: The study discusses the response of a patient with the TP53 Y220C mutation to the M6620-carboplatin combination therapy, suggesting that this variant may correlate with treatment response, which fits the predictive evidence type.

Diagnostic, Prognostic evidence:

Diagnostic: The study assesses the association between GNA14 expression levels and clinicopathological features, indicating its potential use as a biomarker for diagnosis in hepatocellular carcinoma (HCC).

Prognostic: The study identifies low expression of GNA14 as an independent predictor for survival outcomes in patients with HCC, suggesting its role in prognostic assessment.

Prognostic evidence:

Prognostic: The study indicates that miR-28-5p serves as an independent indicator for overall survival in patients with colon cancer, suggesting a correlation between the variant and disease outcome.

Prognostic evidence:

Prognostic: The study indicates that high HOTTIP expression is associated with worse outcomes in cancer patients, specifically noting a pooled hazard ratio of 2.34 for overall survival, which demonstrates a correlation with disease outcome independent of therapy. Additionally, the findings suggest that elevated HOTTIP expression correlates with advanced clinical stage and lymph node metastasis, further supporting its role as a prognostic marker.

Oncogenic evidence:

Oncogenic: The study discusses how alterations in the SPOP gene significantly co-occur with alterations in the BIN1 gene and how somatic mutations in SPOP derange BIN1 gene expression, indicating that SPOP contributes to tumor development or progression in prostate cancer. Additionally, the increased expression of SPOP is associated with reduced survival, further supporting its role in oncogenesis.

Predictive, Prognostic evidence:

Prognostic: The study reports that various mutations, including RNF43-MT, CREBBP-MT, and others, are associated with longer overall survival (OS) in colorectal cancer patients treated with immune checkpoint inhibitors, indicating a correlation between these variants and disease outcome independent of therapy. The abstract specifically mentions hazard ratios (HR) and confidence intervals (CI) that support this association with survival.

Predictive: The abstract discusses the predictive value of specific gene mutations on the overall survival of colorectal cancer patients treated with immune checkpoint inhibitors, indicating that certain mutations may correlate with treatment response. The mention of "predictive biomarkers" and their influence on survival outcomes in the context of therapy supports this classification.

Prognostic evidence:

Prognostic: The abstract indicates that the gene expression and methylation of SERPINA5 and TIMP1 may serve as prognostic predictors in low-grade gliomas (LGGs), suggesting a correlation with disease outcome independent of therapy.

nan evidence:

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nan evidence:

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Predictive, Oncogenic evidence:

Predictive: The study indicates that the F691L mutation confers moderate resistance to gilteritinib, suggesting a correlation between this variant and treatment response. The mention of "resistance" in relation to gilteritinib treatment highlights its predictive nature regarding therapy outcomes.

Oncogenic: The identification of the F691L mutation as a secondary mutation that contributes to resistance implies its role in tumor progression or development, particularly in the context of FLT3 mutations in acute myeloid leukemia. This supports the classification of F691L as an oncogenic variant due to its involvement in resistance mechanisms.

Predictive evidence:

Predictive: The study identifies PPP2R2A deficiency as a potential new predictive biomarker for patient stratification in the clinical use of ATR and CHK1 inhibitors, indicating that this variant correlates with sensitivity to these therapies. The findings suggest that the presence of PPP2R2A deficiency can influence treatment outcomes with ATR and CHK1 inhibitors in non-small cell lung cancer.

Prognostic evidence:

Prognostic: The study reports that patients with a high mutant/wild-type (wt) ratio of FLT3-ITD mutations had significantly shorter overall and disease-free survival, indicating that this variant correlates with disease outcome independent of therapy. The multivariate analysis further supports the high mutant/wt ratio as a strong independent prognostic factor.

Prognostic evidence:

Prognostic: The abstract indicates that TGFbeta2 expression is significantly correlated with patient outcome in multiple types of cancer, particularly gastric cancer, suggesting its role as a prognostic biomarker. This correlation with outcome, independent of therapy context, supports the classification as prognostic evidence.

Prognostic evidence:

Prognostic: The study reports a significant correlation between high EID3 expression and poor overall survival (OS) in glioblastoma multiforme (GBM) patients, indicating that EID3 expression can serve as an independent factor for predicting prognosis. The multivariate Cox regression analysis further supports this association with a specific hazard ratio (HR = 1.41), emphasizing its relevance to disease outcome.

Predictive, Oncogenic evidence:

Predictive: The study indicates that the D816 V mutant c-kit does not respond to STI571, suggesting that this variant correlates with resistance to this specific therapy. The mention of STI571's ineffectiveness against the D816 V variant highlights its predictive nature regarding treatment response.

Oncogenic: The D816 V mutation is implicated in systemic mastocytosis, indicating that it contributes to tumor development or progression. The context of the variant being associated with a disease characterized by abnormal mast cell accumulation supports its classification as oncogenic.

Predictive, Diagnostic evidence:

Predictive: The study suggests that NRG1 and ERBB3 expression may serve as biomarkers for response to SINE treatment, indicating a correlation between these variants and sensitivity to therapy. The mention of the antitumor effect of SINE being influenced by NRG1 and ERBB3 highlights their potential role in predicting treatment outcomes.

Diagnostic: The findings indicate that NRG1 and ERBB3 expression levels can classify ovarian cancer cell lines based on their response to SINE treatment, suggesting their use as biomarkers for identifying SINE-resistant cancers. This classification aligns with the diagnostic evidence type as it relates to defining a subtype of cancer based on variant expression.

Predictive, Prognostic, Oncogenic evidence:

Prognostic: The study indicates that EPS8L3 is associated with poor prognosis in liver cancer, as evidenced by the statement that high expression of EPS8L3 yields poor prognosis in Chinese liver cancer patients.

Oncogenic: The results suggest that EPS8L3 has pivotal oncogenic functions in liver cancer, as it is shown to contribute to cell proliferation and migration, and its knockdown inhibits these processes, indicating its role in tumor development.

Predictive: The findings demonstrate that EPS8L3 expression can substantially increase the efficacy of low dosage Sorafenib treatment, suggesting a correlation between EPS8L3 levels and response to this specific therapy.

Prognostic, Oncogenic evidence:

Oncogenic: The study indicates that CDCA2 acts as an oncogene, as it is overexpressed in prostate cancer and its silencing represses tumor growth, suggesting its role in tumor development and progression.

Prognostic: The abstract mentions that CDCA2 correlates with poor prognosis and patient survival, indicating its potential as a prognostic biomarker in multiple cancer types.

Prognostic evidence:

Prognostic: The study indicates that HHLA2 levels were positively correlated with survival rates in kidney clear cell carcinoma (KIRC), suggesting that it may serve as a prognostic marker for patient outcomes independent of therapy. The mention of "predicts a favorable survival outcome" further supports this classification.

Predictive, Oncogenic evidence:

Oncogenic: The study indicates that Rab18 functions as an oncoprotein in human head and neck squamous cell carcinoma (HNSCC), suggesting that it contributes to tumor development and progression. The mention of Rab18's role in regulating cell proliferation and invasion further supports its oncogenic potential.

Predictive: The abstract states that Rab18 influences cisplatin sensitivity in HNSCC, indicating a correlation between the variant and response to a specific therapy. This suggests that Rab18 may play a role in determining how well patients respond to cisplatin treatment.

Predictive evidence:

Predictive: The abstract indicates that RBM17 is a potential therapeutic target for HCC treatment, suggesting a correlation between the variant and response to therapy. This implies that the variant may influence treatment outcomes, fitting the predictive evidence type.

Prognostic evidence:

Prognostic: The study indicates that PALB2 deletion is significantly associated with shorter disease-free survival (DFS) and overall survival (OS) in colorectal cancer (CRC) patients, suggesting that it serves as an independent prognostic factor for poor outcomes. The multivariate analysis further supports this by confirming that both PALB2 deletion and low mRNA expression are independent prognostic factors of poor OS.

Prognostic evidence:

Prognostic: The abstract mentions a "significant association of higher expression of the COL6A3 E5-E6 junction... with better overall survival," indicating that this variant correlates with disease outcome independent of therapy.

Diagnostic, Predisposing evidence:

Predisposing: The abstract describes Wiedemann-Steiner Syndrome (WSS) as an autosomal dominant disorder, indicating that the KMT2A mutations are inherited and confer a risk for developing this syndrome. The mention of "de novo KMT2A missense mutation" suggests a genetic predisposition to the disorder.

Diagnostic: The identification of heterozygous KMT2A mutations as the molecular defect underlying WSS indicates that these mutations are used to define and classify the disorder, supporting their role as a diagnostic marker for the syndrome.

Predictive, Prognostic evidence:

Prognostic: The study reports that patients with MPC1 deletion tumors have worse overall survival compared to those with MPC1 intact tumors, indicating a correlation between the variant and disease outcome independent of therapy.

Predictive: The results indicate that MPC1 deletion is associated with a poor response to temozolomide (TMZ) chemotherapy in glioblastoma patients, suggesting that the variant may influence treatment sensitivity.

nan evidence:

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Predictive, Oncogenic evidence:

Predictive: The study discusses the treatment of patients with tumors harboring FGFR aberrations with the FGFR inhibitor AZD4547, indicating a correlation between the presence of these variants and the response to therapy, as evidenced by the reported response rates and progression-free survival metrics.

Oncogenic: The abstract mentions that different FGFR somatic alterations may confer varying levels of signaling potency and oncogene dependence, suggesting that these variants contribute to tumor development or progression.

Predictive, Oncogenic evidence:

Predictive: The study discusses the treatment of patients with tumors harboring FGFR aberrations with the FGFR inhibitor AZD4547, indicating a correlation between the presence of these variants and the response to therapy, as evidenced by the reported response rates and progression-free survival metrics.

Oncogenic: The abstract mentions that different FGFR somatic alterations may confer varying levels of signaling potency and oncogene dependence, suggesting that these variants contribute to tumor development or progression.

Predictive, Oncogenic evidence:

Predictive: The study discusses how the loss of the RB tumor suppressor correlates with increased drug sensitivity to specific therapies, particularly CHK inhibitors, indicating a potential for targeted treatment in RB-deficient triple-negative breast cancers (TNBCs). The mention of "therapeutic effects were robust and selective for RB loss of function" further supports this classification.

Oncogenic: The abstract indicates that approximately 30% of TNBCs exhibit functional loss of the RB tumor suppressor, suggesting that this loss contributes to tumor development and progression, particularly through the mechanisms of checkpoint functions and increased sensitivity to therapies. The context of RB loss being a target for precision intervention implies its role in oncogenesis.

Predisposing, Functional evidence:

Predisposing: The study discusses germline variants of WWP1, including K740N, which are associated with a hereditary predisposition to multiple types of cancer, indicating that these variants confer inherited risk for developing disease.

Functional: The results indicate that the prioritized WWP1 variants, including K740N, resulted in gain-of-function effects that led to aberrant enzymatic activation and consequent PTEN inactivation, demonstrating an alteration in molecular function.

Predictive, Oncogenic evidence:

Predictive: The study discusses how KRAS mutations, specifically G12D and G12V, correlate with increased sensitivity to metformin treatment in colorectal cancer (CRC) cell lines, indicating that these variants may predict a better therapeutic response to this drug.

Oncogenic: The presence of KRAS mutations (G12D and G12V) is implicated in enhancing the tumor cells' sensitivity to metformin, suggesting that these somatic variants contribute to tumor development or progression by altering the response to therapy.

Oncogenic evidence:

Oncogenic: The abstract discusses how the E542K mutation, along with other PI3-kinase mutations, induces oncogenic transformation in chicken embryo fibroblasts, demonstrating its role in tumor development. The evidence of elevated catalytic activity and constitutive phosphorylation of key signaling proteins further supports its oncogenic potential.

Predictive, Diagnostic, Oncogenic, Functional evidence:

Predictive: The study provides evidence that somatic mutations in the EGFR gene's TK domain are associated with sensitivity to gefitinib and erlotinib, as indicated by the significant differences in mutation presence between gefitinib-sensitive and refractory tumors. This correlation suggests that the presence of these mutations can predict the response to these specific therapies.

Diagnostic: The abstract mentions that most mutation-positive tumors were adenocarcinomas from never smokers, indicating that these mutations can be used to classify a specific subtype of lung cancer. This association supports the use of EGFR mutations as a diagnostic marker for identifying a distinct subset of lung cancers.

Oncogenic: The presence of somatic mutations in the EGFR TK domain is implicated in the development of lung cancer, as the study discusses the mutations found in tumors and their association with sensitivity to targeted therapies. This suggests that these mutations contribute to tumor development or progression in the context of lung cancer.

Functional: The study describes how specific mutations in the EGFR TK domain alter the molecular function of the protein, as evidenced by the differences in phosphotyrosine levels and drug sensitivity in the mutant forms compared to the wild-type. This indicates that the mutations have a direct impact on the biochemical activity of the EGFR protein.

Oncogenic, Functional evidence:

Oncogenic: The study demonstrates that PHGDH knockdown significantly inhibited cell viability, colony formation, and tumor growth in thyroid cancer cell lines and in vivo models, indicating that PHGDH contributes to tumor development and progression in papillary thyroid cancer.

Functional: The results show that PHGDH inhibition affects the expression of embryonic cancer stemness markers and alters cell viability and colony formation, suggesting that the variant alters molecular function related to tumorigenesis in thyroid cancer.

Diagnostic, Functional evidence:

Diagnostic: The abstract mentions that mutated ACVR2A is significantly associated with MSI-H in gastric cancer (GC), indicating its potential use as a biomarker for classification or diagnosis of this subtype.

Functional: The results section describes the generation of stable cell lines overexpressing ACVR2A and its mutants, which implies that the variants, including c.1310delA, are being studied for their molecular function and effects on protein expression.

Predictive, Oncogenic evidence:

Predictive: The study investigates how mutations in the AXL receptor, specifically tyrosine 821, contribute to resistance against cetuximab and radiation treatment in head and neck squamous cell carcinoma (HNSCC). The findings suggest that targeting AXL and c-ABL can overcome this resistance, indicating a correlation between the variant and treatment response.

Oncogenic: The research highlights that the signaling of AXL, particularly through the mutation of tyrosine 821, plays a role in the development of resistance in HNSCC, suggesting that this variant contributes to tumor progression and behavior in the context of cancer treatment.

Prognostic, Oncogenic evidence:

Prognostic: The study reports that high mRNA levels of HOXA2, HOXA3, and HOXA13, as well as low levels of HOXA7, predict poor overall survival (OS) of KIRC patients, indicating a correlation between these variants and disease outcome independent of therapy.

Oncogenic: The findings suggest that HOXA13 functions as a novel oncogene in KIRC, as the knockdown of HOXA13 significantly suppressed cell proliferation in vitro, demonstrating its role in tumor development or progression.

Predictive evidence:

Predictive: The study discusses the administration of gemtuzumab ozogamycin (mylotarg) in patients with untreated acute promyelocytic leukemia (APL) and reports a complete remission (CR) rate of 84%, indicating that the variant correlates with response to this specific therapy. The mention of treatment response and the effectiveness of mylotarg in achieving CR supports this classification.

Predictive, Oncogenic evidence:

Predictive: The study discusses how patients with KRAS G12C-mutant non-small cell lung cancer (NSCLC) experience clinical benefit from selective KRAS G12C inhibition, indicating a correlation between the variant and response to therapy. Additionally, it highlights the resistance mechanisms in colorectal cancer, suggesting that the variant's presence influences treatment outcomes.

Oncogenic: The variant KRAS G12C is implicated in tumor development, as the study examines its role in colorectal cancer cell lines and discusses the effects of KRAS G12C inhibition, which is indicative of its contribution to cancer progression. The findings suggest that KRAS G12C is a driver mutation in these cancer types.

Prognostic evidence:

Prognostic: The abstract states that "STAT1 has been identified to have prognostic value in patients with solid cancer," indicating that the variant correlates with disease outcome independent of therapy. Additionally, the mention of "predict prognosis in cancer patients based on their tumor types" further supports its prognostic significance.

Prognostic, Oncogenic evidence:

Oncogenic: The abstract states that "LncRNA SNHG4 has been reported to be an oncogenic lncRNA in osteosarcoma" and confirms its upregulation in glioblastoma (GBM), indicating that SNHG4 contributes to tumor development or progression in this context. Additionally, the mention of SNHG4's role in promoting the proliferation of GBM cells further supports its oncogenic nature.

Prognostic: The abstract notes that "lower survival rate of GBM patients was observed in patients with high SNHG4 expression level," suggesting that the expression level of SNHG4 correlates with disease outcome, specifically survival, independent of therapy.

Predictive, Prognostic evidence:

Predictive: The study indicates that Nek1 knockdown sensitized cancer cells to ionizing radiation, suggesting a correlation with treatment response, particularly in the context of radiation therapy.

Prognostic: The results show that elevated levels of Nek1 were associated with impaired cancer-specific and overall survival, indicating its potential role as a prognostic marker for disease outcome in cervical cancer patients.

Predictive, Diagnostic evidence:

Predictive: The study identifies PTEN gene copy number loss as a promising mechanistic biomarker predictive of cetuximab resistance in head and neck squamous cell carcinoma (HNSCC), indicating that this variant correlates with resistance to the therapy. The mention of "predictive of cetuximab resistance" directly supports this classification.

Diagnostic: The abstract discusses the prevalence of PTEN gene copy number loss in HNSCC, suggesting its potential use as a biomarker for identifying patients who may not respond to cetuximab treatment. This aligns with the diagnostic evidence type as it relates to classifying a disease subtype based on the presence of the variant.

Predictive, Diagnostic evidence:

Predictive: The study indicates that CXCR7 is a critical regulator of prostate cancer sensitivity to enzalutamide, suggesting a correlation between the variant and resistance to this specific therapy. The mention of "therapeutic potential of MAPK/ERK inhibitors" further supports the predictive nature of the findings regarding treatment response.

Diagnostic: The findings suggest that CXCR7 may serve as a biomarker of resistant disease in patients with prostate cancer, indicating its role in classifying or defining a subtype of the disease, particularly in the context of enzalutamide resistance.

Predictive, Functional evidence:

Predictive: The study discusses the correlation between miR-200c-3p expression and progression-free survival (PFS) in patients undergoing EGFR-TKI treatment, indicating that higher expression is associated with longer PFS, which suggests a predictive role in therapy response.

Functional: The research demonstrates that miR-200c-3p overexpression inhibits the epithelial-to-mesenchymal transition (EMT) process and promotes cell death in EGFR TKI-resistant cell lines, indicating that this variant alters molecular function related to drug sensitivity.

Predictive, Diagnostic evidence:

Predictive: The study identifies that cell lines with activating PIK3CA mutations or loss of PTEN expression are more resistant to cetuximab, indicating that these mutations correlate with treatment response. This suggests that the mutation status of these genes could serve as a predictive biomarker for cetuximab sensitivity in colorectal cancer.

Diagnostic: The examination of mutation status of signaling components downstream of EGFR, such as PIK3CA and PTEN, is used to classify the sensitivity or resistance of colon cancer cell lines to cetuximab. This classification based on mutation status supports the use of these variants as biomarkers for determining patient eligibility for cetuximab therapy.

Predictive, Oncogenic evidence:

Predictive: The abstract mentions that the progression-free survival (PFS) benefit of everolimus was maintained irrespective of PIK3CA genotypes, indicating that the variant E542K may not affect the response to this therapy, which is a predictive aspect of the variant's role in treatment outcomes.

Oncogenic: The results section discusses how PIK3CA mutations, including E542K, contribute to aberrant signaling in the PI3K/AKT/mTOR pathway, which is implicated in tumorigenesis and progression, thus supporting the oncogenic nature of this variant.

Predictive, Oncogenic evidence:

Oncogenic: The abstract discusses TRK fusions as oncogenic drivers in various tumor types, indicating that these genetic alterations contribute to tumor development. The results section confirms the presence of a brain tumor with specific cellular characteristics, and the mention of BRAF V600E being negative suggests that the study is focused on the oncogenic role of other variants rather than V600E itself.

Predictive: The abstract highlights the successful treatment of a TRK fusion-driven HGG with larotrectinib, a selective pan-TRK inhibitor, indicating a correlation between the presence of the TRK fusion and the response to this specific therapy. This suggests that the variant plays a predictive role in treatment outcomes.

Predictive, Oncogenic evidence:

Predictive: The Gly101Val mutation in BCL2 is associated with resistance to venetoclax in patients, indicating that this variant correlates with treatment response and highlights its role in therapeutic resistance.

Oncogenic: The acquisition of the Gly101Val mutation is linked to the development of resistance in chronic lymphocytic leukemia, suggesting that this somatic variant contributes to tumor progression and treatment failure.

Predictive evidence:

Predictive: The study assesses the efficacy of ivosidenib, a targeted inhibitor of mutated IDH1, in patients with IDH1-mutant cholangiocarcinoma, indicating that the presence of the IDH1 mutation correlates with improved progression-free survival when treated with this therapy. The results show a significant improvement in progression-free survival with ivosidenib compared to placebo, highlighting the predictive nature of the IDH1 mutation in response to treatment.

Predictive, Diagnostic evidence:

Predictive: The study discusses the sensitivity of ASS1-deficient ovarian cancer cells to the arginine-depriving therapeutic ADI-PEG20, indicating a correlation with treatment response. This suggests that the variant's status may predict the effectiveness of this specific therapy in treating SCCOHT and other ovarian cancer subtypes.

Diagnostic: The abstract mentions that low ASS1 expression was validated through immunohistochemistry (IHC) in large patient cohorts, indicating that ASS1 deficiency can be used to classify or define certain ovarian cancer subtypes, including SCCOHT. This establishes a diagnostic role for the variant in identifying patients with these rare cancer types.

Predictive, Oncogenic evidence:

Oncogenic: The ETV6-NTRK3 gene fusion is described as a "potent oncogenic driver" in infantile fibrosarcoma (IFS), indicating its role in tumor development and progression.

Predictive: The study reports a "very rapid, complete, and sustained response" of chemotherapy-refractory IFS to the TRK inhibitor larotrectinib, demonstrating that the presence of the ETV6-NTRK3 fusion correlates with a positive therapeutic response to this specific treatment.

Predictive, Oncogenic evidence:

Oncogenic: The abstract discusses the link between the Fli-1 signaling network and oncogenesis in glioblastoma multiforme (GBM), indicating that Fli-1 is associated with tumor development and progression, particularly in the context of radio/TMZ-resistant GBM.

Predictive: The study highlights that lumefantrine, identified as a Fli-1 inhibitor, promotes growth suppression and apoptosis in both parental and radio/TMZ-resistant GBM, suggesting its potential as a therapeutic agent that correlates with response to treatment.

Oncogenic, Functional evidence:

Oncogenic: The MPL Y252H mutation is described as a "disease-driving mutation" that contributes to the development of essential thrombocythemia (ET), indicating its role in tumor progression. The evidence of increased TPO/MPL-mediated cell growth and survival upon cytokine withdrawal further supports its oncogenic potential.

Functional: The study demonstrates that the Y252H mutation results in increased sensitivity to thrombopoietin (TPO) and enhanced cell growth and survival, indicating that it alters the molecular function of the MPL receptor. This functional alteration is evidenced by the in vitro assays conducted with BaF3 cells.

Prognostic evidence: