Predictive, Functional evidence:

Functional: The abstract discusses how the HER2(YVMA) mutant transphosphorylates kinase-dead EGFR(K721R) and EGFR(WT), indicating that the K721R variant alters the molecular function of the EGFR protein in the presence of HER2 mutations and tyrosine kinase inhibitors. This suggests a change in biochemical activity related to the variant.

Predictive: The study mentions that cancer cells expressing the HER2(YVMA) mutation remain sensitive to HER2-targeted therapies but are insensitive to EGFR TKIs, indicating that the K721R variant's presence correlates with treatment response, specifically in the context of therapy with HER2 inhibitors.

nan evidence:

Missing abstract

Predictive, Prognostic evidence:

Prognostic: The study indicates that DNMT3A mutations, particularly those at the R882 position, are associated with a poor outcome in acute myeloid leukemia (AML) patients, suggesting a correlation with disease progression and overall survival.

Predictive: The findings suggest that DNMT3A mutations, including those at the R882 position, could serve as predictive factors for response to idarubicin treatment, indicating their potential role in guiding therapy decisions for AML patients.

Predictive, Functional evidence:

Predictive: The study discusses the imatinib sensitivity associated with the CSF1R-Y571D mutation, indicating that this variant correlates with a response to therapy, specifically imatinib treatment.

Functional: The Y571D variant is shown to result in increased colony growth and constitutive phosphorylation of CSF1R, demonstrating that it alters the molecular function of the receptor, which is supported by the experimental findings in the cell line GDM1.

Diagnostic, Oncogenic evidence:

Diagnostic: The study discusses the KRAS mutation analysis as a predictive biomarker in colorectal cancer, indicating that the presence of specific mutations, including glycine to aspartate, is essential for defining the mutational status of tumors prior to treatment. This establishes the variant's role in classifying and confirming the disease subtype.

Oncogenic: The presence of the glycine to aspartate mutation in codon 12 is highlighted as a frequent mutation in colorectal cancer, suggesting its contribution to tumor development and progression, which aligns with the definition of oncogenic variants.

Oncogenic evidence:

Oncogenic: The study discusses ras-gene mutations occurring in a significant percentage of adenomas and carcinomas, indicating that these mutations contribute to tumor development and progression in colorectal cancer. The accumulation of these molecular alterations aligns with the clinical progression of tumors, supporting the role of these mutations in oncogenesis.

Oncogenic evidence:

Oncogenic: The abstract discusses the role of Notch in neoplasias, indicating that Notch can act as an oncogene or tumor suppressor, which suggests that variants in the Notch signaling pathway may contribute to tumor development or progression. This aligns with the definition of oncogenic evidence, as it implies a direct involvement in cancer biology.

Functional evidence:

Functional: The abstract states that "functional analysis showed no alteration compared to non-mutated BCR-ABL," indicating that the K247R variant does not change the molecular or biochemical function of the BCR-ABL protein. This suggests that the variant's presence does not affect the protein's activity or behavior in a significant way.

Predictive, Diagnostic evidence:

Predictive: The study indicates that the presence of the T315I mutation is predictive of relapse despite a molecular response to imatinib, suggesting that monitoring this variant can inform therapeutic management decisions.

Diagnostic: The analysis of T315I mutated BCR-ABL clones throughout the CML history of patients suggests that this variant can be used to classify and monitor the disease progression in chronic myeloid leukemia (CML).

Predictive, Functional evidence:

Predictive: The study discusses the Thr315Ile mutation in the context of resistance to the tyrosine kinase inhibitor STI571 in chronic myeloid leukemia (CML), indicating that this variant correlates with treatment resistance, which is a key aspect of predictive evidence.

Functional: The presence of the Thr315Ile mutation is associated with clonal selection due to the functional inhibiting effect of STI571, suggesting that this variant alters the molecular response to the therapy, which aligns with functional evidence.

nan evidence:

Missing abstract

Predictive, Diagnostic, Oncogenic evidence:

Diagnostic: The study identifies the Glu255Lys mutation in patients with Ph+ acute lymphoblastic leukemia (ALL), suggesting its role in classifying or confirming the disease prior to treatment with STI571.

Predictive: The presence of the Glu255Lys mutation is associated with the development of resistance to STI571 treatment, indicating that it may predict treatment response or resistance in patients with Ph+ ALL.

Oncogenic: The Glu255Lys mutation is described as an oncogenic variant that contributes to the development of resistance in leukemic cells, highlighting its role in tumor progression.

Predictive evidence:

Predictive: The abstract discusses how the T315I variant is resistant to the therapies dasatinib and nilotinib, indicating that it correlates with resistance to these specific treatments. The mention of T315I being the only mutant isolated at drug concentrations equivalent to maximal achievable plasma trough levels further emphasizes its role in treatment resistance.

nan evidence:

Missing abstract

Predictive, Diagnostic evidence:

Predictive: The abstract discusses the importance of the BCR-ABL mutation profile in determining the response to second-generation tyrosine kinase inhibitors (TKIs) like dasatinib and nilotinib, indicating that certain mutations correlate with treatment efficacy. This suggests that the variant's presence can influence the choice of therapy and its expected success, which aligns with predictive evidence.

Diagnostic: The mention of the BCR-ABL mutation profile as a factor in treatment decisions implies that these mutations are used to classify or define the patient's disease state, particularly in the context of chronic myeloid leukemia and resistance to imatinib therapy. This supports the classification of the variant as diagnostic.

Predictive evidence:

Predictive: The study identifies EGFR mutations as the strongest predictive biomarker for progression-free survival (PFS) and tumor response to gefitinib compared to carboplatin/paclitaxel, indicating a correlation between the presence of these mutations and treatment efficacy. The results highlight that the predictive value of EGFR gene copy number is influenced by the presence of coexisting EGFR mutations, further supporting the predictive nature of these biomarkers in treatment response.

Diagnostic, Functional evidence:

Diagnostic: The study discusses the c.38G>A KRAS mutation in the context of mutation detection methods, indicating its role in distinguishing true mutations from artefacts, which suggests its use in defining or confirming a disease or subtype.

Functional: The mention of the c.38G>A variant in the context of mutation detection implies that it may alter the molecular function of the KRAS protein, as the study focuses on the sensitivity of detecting this specific mutation through various methods.

Predictive, Diagnostic evidence:

Diagnostic: The abstract states that "neither mutation of EGFR nor increased copy number of EGFR or HER2 was diagnostic of response to gefitinib," indicating that the presence of the L858R variant does not serve as a reliable biomarker for treatment response, which aligns with the definition of diagnostic evidence.

Predictive: The abstract mentions the need for "additional predictive biomarkers beyond EGFR status," suggesting that while the L858R variant is not predictive of response to gefitinib, it is still discussed in the context of treatment outcomes, which fits the predictive evidence type.

Predictive, Oncogenic evidence:

Predictive: The study discusses how mutant EGFRs in NSCLCs correlate with resistance to conventional chemotherapeutic drugs and sensitivity to gefitinib, indicating that these variants influence treatment response. The mention of "inhibition of those signals by gefitinib may contribute to the drug's efficacy" further supports this classification.

Oncogenic: The abstract describes how mutant EGFRs promote cell survival and are involved in signaling pathways that contribute to tumor development, indicating their role in oncogenesis. The activation of specific signaling pathways by these mutations suggests they contribute to tumor progression in NSCLC.

Predictive, Functional evidence:

Predictive: The study identifies specific mutations in the EGFR gene that correlate with clinical responsiveness to the tyrosine kinase inhibitor gefitinib, indicating that these mutations are associated with sensitivity to this therapy. The results show that patients with these mutations had a rapid and dramatic clinical response to gefitinib, supporting the predictive nature of the variant in treatment outcomes.

Functional: The identified EGFR mutations demonstrated enhanced tyrosine kinase activity in response to epidermal growth factor and increased sensitivity to gefitinib in vitro, indicating that these mutations alter the molecular function of the EGFR protein. This functional alteration is critical for understanding how these mutations contribute to the observed therapeutic responses.

Predictive, Oncogenic evidence:

Predictive: The abstract states that "classical mutations in the EGFR tyrosine kinase domain... have been associated with sensitivity to tyrosine kinase inhibitors (TKIs) in patients with NSCLC," indicating that the L858R mutation correlates with response to therapy. Additionally, the results section mentions that "somatic mutations in the tyrosine kinase domain of the EGFR gene... were significantly correlated with clinical response to gefitinib therapy," further supporting the predictive nature of this variant in relation to treatment outcomes.

Oncogenic: The abstract discusses "classical mutations" in the EGFR gene, including L858R, which are known to contribute to tumor development in non-small cell lung cancer (NSCLC). This classification is supported by the context of the study focusing on mutations that drive cancer progression and their association with treatment response.

Predictive evidence:

Predictive: The presence of a mutation in the epidermal growth factor receptor gene (EGFR) is described as a strong predictor of a better outcome with gefitinib, indicating that the variant correlates with response to this specific therapy. The results show that patients with the EGFR mutation had significantly longer progression-free survival when treated with gefitinib compared to those treated with carboplatin-paclitaxel.

Oncogenic evidence:

Oncogenic: The study identifies the L861Q mutation in the EGFR kinase domain as a rare event in glioblastomas, indicating its potential role in tumor development or progression, particularly as it is located in a region associated with mutations in lung cancer. This suggests that the variant may contribute to oncogenic processes in this context.

Predictive, Oncogenic evidence:

Predictive: The abstract discusses how the B-RAFV600E mutation predicts a dependency on the MAPK signaling cascade in melanoma, which is further supported by the success of RAF and MEK inhibitors in clinical trials. This indicates a correlation between the variant and response to specific therapies.

Oncogenic: The abstract mentions that oncogenic mutations in B-RAF, including B-RAFV600E, are found in a significant percentage of malignant melanomas, suggesting that this variant contributes to tumor development or progression. Additionally, the results section describes the use of B-RAFV600E cell lines to study resistance mechanisms, further supporting its role in oncogenesis.

Oncogenic evidence:

Oncogenic: The study demonstrates that gain-of-function BRAF signaling is strongly associated with in vivo tumorigenicity, indicating that the BRAF variant contributes to tumor development and progression. This is supported by the evidence of tumor regression upon BRAF suppression in xenograft models, which highlights its role in promoting tumor cell proliferation and survival.

Predictive, Oncogenic evidence:

Predictive: The study discusses the response of patients with the V600E BRAF mutation to the drug PLX4032, indicating that treatment led to partial or complete tumor regression in a significant number of patients. This suggests a correlation between the presence of the V600E mutation and the effectiveness of the therapy, which is a key aspect of predictive evidence.

Oncogenic: The V600E mutation in BRAF is identified as a somatic mutation that contributes to tumor development in melanoma, as the study focuses on patients with this specific mutation and its role in the context of targeted therapy. This aligns with the definition of oncogenic evidence, as the mutation is implicated in the progression of the disease.

Oncogenic evidence:

Oncogenic: The study discusses various B-RAF mutations, indicating that they contribute to tumor development by showing elevated kinase activity and signaling to ERK, which is a hallmark of oncogenic behavior. The mention of the activation of C-RAF and the role of these mutations in converting B-RAF into an active conformation further supports their oncogenic potential.

Predictive evidence:

Predictive: The study discusses the effects of the multikinase inhibitor INNO-406 on cells harboring the KIT mutant V560G, indicating that the presence of this variant may influence the response to therapy, as evidenced by the differential inhibition of proliferation in HMC-1.1 cells compared to HMC-1.2 cells. This suggests a correlation between the V560G variant and sensitivity to the drug, which aligns with the predictive evidence type.

Predictive, Diagnostic, Oncogenic evidence:

Predictive: The D816V substitution in the activation loop of KIT results in relative resistance to the kinase inhibitor imatinib (Gleevec), indicating that this variant correlates with treatment response.

Diagnostic: The D816V mutation occurs in 80 to 95% of adult systemic mastocytosis (SM) cases, highlighting its significance in the detection and diagnosis of this disease.

Oncogenic: The abstract discusses oncogenic mutations of the receptor tyrosine kinase KIT, including D816V and D816F, which contribute to the pathogenesis of gastrointestinal stromal tumors and systemic mastocytosis, indicating their role in tumor development.

Oncogenic evidence:

Oncogenic: The study reports that somatic c-KIT mutations, specifically the substitution of valine for aspartate at codon 816, are characteristic of sporadic adult mastocytosis and contribute to the spontaneous activation of the mast cell growth factor receptor, indicating a role in tumor development or progression.

Predictive, Oncogenic evidence:

Oncogenic: The study indicates that activating mutations in KIT, including D816V, may contribute to tumorigenesis in a subset of seminomas, suggesting a role in tumor development or progression. This is supported by the observation of constitutive phosphorylation of the mutant isoforms, indicating their involvement in oncogenic signaling pathways.

Predictive: The abstract mentions that D816V and D816H were resistant to imatinib mesylate, which implies a correlation with resistance to this specific therapy. This suggests that the presence of these mutations can predict the response to treatment with imatinib.

Predictive, Prognostic evidence:

Predictive: The study examines the correlation between mutations in KIT and PDGFRA and clinical response to imatinib, indicating that the mutational status of these oncoproteins is predictive of clinical response to the therapy. Specifically, it reports that patients with exon 11 KIT mutations had a significantly higher partial response rate to imatinib compared to those with exon 9 mutations or no detectable mutations.

Prognostic: The results indicate that patients with tumors containing exon 11 KIT mutations had a longer event-free and overall survival compared to those with exon 9 mutations or no detectable mutations, suggesting that this variant correlates with better disease outcomes independent of therapy.

Predictive, Oncogenic evidence:

Predictive: The abstract discusses how secondary mutations in the target kinase contribute to acquired resistance to tyrosine kinase inhibitors, indicating a correlation between these mutations and treatment response. This suggests that the variant may influence sensitivity or resistance to specific therapies.

Oncogenic: The mention of KIT and PDGFRA mutations being involved in the pathogenesis of gastrointestinal stromal tumors indicates that these somatic variants contribute to tumor development or progression. This aligns with the definition of oncogenic variants as they are implicated in cancer biology.

Oncogenic evidence:

Oncogenic: The study identifies oncogenic mutations in the KIT gene in a significant proportion of melanoma tumors, indicating that these mutations contribute to tumor development in specific melanoma subtypes. The presence of KIT mutations and their association with increased protein levels further supports the role of KIT as an important oncogene in melanoma.

Oncogenic evidence:

Oncogenic: The study discusses gain-of-function mutations in the c-kit gene, specifically noting that the mutant KIT exhibited constitutive phosphorylation and strong kinase activity, which are indicative of its role in tumor development and progression. The ability of the transfectant to grow autonomously and form tumors in nude mice further supports the oncogenic nature of the variant.

Predictive, Prognostic evidence:

Predictive: The study demonstrates that the V560G variant of Kit shows increased sensitivity to Imatinib, with a lower GI50 compared to wild-type Kit, indicating a correlation with treatment response. This suggests that the presence of the V560G mutation may predict a better response to Imatinib therapy in gastrointestinal stromal tumors.

Prognostic: The abstract mentions that mutations in the juxtamembrane region of Kit, including V560G, have been linked to poor prognosis in gastrointestinal stromal tumors, indicating that this variant may correlate with disease outcome independent of therapy.

Oncogenic evidence:

Oncogenic: The study discusses mutations in the c-kit proto-oncogene, specifically the substitutions of Gly-560 for Val and Val-816 for Asp, which are implicated in the constitutive activation of the c-kit receptor. This activation is associated with tumor development in the context of mast cell leukemia, indicating that these mutations contribute to oncogenic processes.

Oncogenic evidence:

Oncogenic: The study demonstrates that the Val-559-->Gly (G559) mutation in the c-kit receptor tyrosine kinase leads to constitutive activation and factor-independent growth in murine pro-B-type cells, indicating that this somatic variant contributes to tumor development and progression. Additionally, the injection of cells expressing KITG559 into nude mice resulted in tumor formation and rapid onset of leukemia, further supporting its oncogenic role.

Functional evidence:

Functional: The study demonstrates that the valine to alanine substitution at residue 536 (V536A) in the PDGFbetaR leads to increased tyrosine kinase activity and allows cells to survive and proliferate without growth factors, indicating that this variant alters the molecular function of the receptor. The findings suggest that the mutation enhances the receptor's activity, which is a clear alteration in biochemical function.

Predictive evidence:

Predictive: The study indicates that the Val559Ile mutation in the c-kit gene is associated with resistance to imatinib therapy, as it was found that imatinib inhibited autophosphorylation of the mutant KIT with Val559Asp but not with Val559Ile. This suggests that the presence of the Val559Ile variant correlates with a lack of response to this specific treatment.

Predictive, Oncogenic evidence:

Predictive: The study assesses the clinical effects of imatinib mesylate in patients with melanoma harboring KIT alterations, indicating a correlation between the presence of these mutations and the response to therapy. The results show that response rates were better in cases with specific mutations, suggesting that these alterations predict sensitivity to treatment with imatinib.

Oncogenic: The abstract discusses activating mutations and amplification of the KIT gene in melanoma, which are implicated in tumor development and progression. The focus on the effects of KIT inhibition further supports the notion that these alterations contribute to the oncogenic process in this subset of melanoma.

Predisposing, Oncogenic evidence:

Oncogenic: The substitution of Glu for Lys(642) is described as an oncogenic mutation in the tyrosine kinase domain of KIT, indicating that it contributes to tumor development or progression, as demonstrated by the proliferation assay and tumor formation in nude mice.

Predisposing: The variant is noted as a germline heterozygous mutation that causes diffuse hyperplasia of myenteric interstitial cells of Cajal during embryonic development and leads to the occurrence of multiple gastrointestinal stromal tumors in adulthood, indicating an inherited risk for developing disease.

Predictive, Oncogenic evidence:

Oncogenic: The study identifies KRAS mutations (G12A and G12V) in thymic tumors, indicating that these somatic variants contribute to tumor development or progression, as they are associated with specific tumor types (thymoma and thymic carcinoma).

Predictive: The results mention that the V560del KIT mutant was associated with similar sensitivities to imatinib and sunitinib, suggesting a correlation between the presence of specific mutations and the response to these therapies, which aligns with predictive evidence.

Oncogenic evidence:

Oncogenic: The study demonstrates that mutations in the c-kit gene lead to the constitutive activation of the KIT protein, which is implicated in the malignant transformation of cells, indicating that these mutations contribute to tumor development. The stable transfection of mutant c-kit DNAs into Ba/F3 cells further supports the oncogenic role of these variants in gastrointestinal stromal tumors (GISTs).

Predictive, Prognostic evidence:

Predictive: The study evaluates the impact of primary and secondary kinase genotype on sunitinib activity, indicating that specific mutations in the KIT gene correlate with clinical benefit and progression-free survival in patients treated with sunitinib after imatinib failure. This suggests that the variant's presence influences the response to therapy, classifying it as predictive evidence.

Prognostic: The results indicate that patients with specific KIT mutations (exon 9 and wild-type) have significantly longer progression-free survival and overall survival compared to those with other mutations, demonstrating that these variants correlate with disease outcomes independent of therapy. This supports the classification as prognostic evidence.

Predictive evidence:

Predictive: The abstract discusses the impact of targeting KIT with tyrosine kinase inhibitors like imatinib and sunitinib in the treatment of gastrointestinal stromal tumors (GISTs), indicating a correlation between the KIT variant and response to these therapies. This suggests that the presence of the KIT variant may influence treatment outcomes, classifying it as predictive evidence.

Predictive, Oncogenic evidence:

Predictive: The study discusses the correlation between KIT mutations and resistance to imatinib therapy in GIST patients, indicating that these mutations are associated with treatment response and resistance. The mention of "imatinib-acquired-resistance" and the investigation of downstream signaling profiles in relation to therapy highlights the predictive nature of the variant's impact on treatment outcomes.

Oncogenic: The presence of activating mutations in the KIT gene, particularly in the context of gastrointestinal stromal tumors, suggests that these mutations contribute to tumor development and progression. The identification of secondary KIT mutations in patients who developed resistance to imatinib further supports the oncogenic role of these variants in GISTs.

Predictive evidence:

Predictive: The study demonstrates that the presence of the KIT exon 11-mutant genotype correlates with improved treatment outcomes in patients treated with imatinib, indicating a relationship between the genotype and response to therapy. This is evidenced by the significantly higher objective response rates and longer time to tumor progression for patients with the exon 11 mutation compared to those with exon 9 mutations and wild-type genotypes.

Predictive, Oncogenic evidence:

Oncogenic: The abstract states that approximately 85% of GISTs have oncogenic mutations in KIT, which are responsible for constitutive kinase activation leading to cellular proliferation and survival. This indicates that the variant contributes to tumor development or progression.

Predictive: The abstract mentions that the progression-free and overall survival of patients with advanced disease is greatly improved by treatment with kinase inhibitors, indicating a correlation between the variant and response to therapy.

Predictive evidence:

Predictive: The study discusses the response rates of patients with various types of CML and gastrointestinal stromal tumors to imatinib treatment, indicating that the BCR-ABL variant correlates with therapeutic response, as evidenced by the reported haematological and cytogenetic responses in patients treated with imatinib.

Predictive, Oncogenic evidence:

Predictive: The study discusses the role of KIT mutations in response to the tyrosine kinase inhibitor imatinib, indicating that these mutations are associated with secondary resistance to therapy. This suggests a correlation between the presence of these mutations and treatment outcomes, which aligns with the predictive evidence type.

Oncogenic: The identification of newly acquired KIT mutations in GISTs suggests that these somatic mutations contribute to tumor progression and resistance to therapy, indicating their role in oncogenesis. The study highlights the presence of these mutations in tumor samples, supporting their classification as oncogenic variants.

Predictive, Oncogenic evidence:

Oncogenic: The study identifies c-kit mutations, including Pro551Leu, as potential gain-of-function mutations that may be involved in the pathogenesis of adenoid cystic carcinoma of the salivary glands, indicating a role in tumor development.

Predictive: The abstract suggests a potential correlation between c-kit mutations, such as Pro551Leu, and the treatment of adenoid cystic carcinoma with tyrosine kinase inhibitors, indicating that this variant may influence treatment response.

Diagnostic, Oncogenic evidence:

Diagnostic: The study discusses the identification of mutations, including p.R822H, in the context of performing mutational analysis in gastrointestinal stromal tumors, indicating its role in defining or confirming the presence of a disease.

Oncogenic: The presence of the p.R822H variant in the context of PDGFRA mutations suggests its potential contribution to tumor development or progression, as it is part of the mutational analysis performed on gastrointestinal stromal tumors.

Oncogenic, Functional evidence:

Functional: The V536E mutation is described as stimulating Ba/F3 cell growth and signaling via ERK and STAT5 in the absence of ligand, indicating that it alters molecular function. This suggests that the mutation has a specific impact on the receptor's activity and signaling pathways.

Oncogenic: The V536E mutation is characterized as a gain-of-function mutant, which implies that it contributes to tumor development or progression, particularly in the context of glioblastoma. This classification is supported by the evidence that the mutation enhances cell growth and signaling, which are key features of oncogenic variants.

Predictive, Prognostic evidence:

Predictive: The study indicates that none of the patients with the D842V substitution had a response to imatinib, suggesting that this variant correlates with resistance to the therapy. Additionally, the median progression-free survival for patients with D842V was significantly lower compared to those with other PDGFRA mutations, further supporting its predictive nature regarding treatment outcomes.

Prognostic: The median overall survival for patients with D842V substitutions was reported as 14.7 months, which provides evidence that this variant correlates with disease outcome independent of therapy. This suggests that the D842V variant may have a prognostic impact on survival in patients with advanced PDGFRA-mutant GISTs.

Oncogenic evidence:

Oncogenic: The study discusses that activating mutations in the KIT receptor tyrosine kinase and intragenic activation mutations in PDGFRA serve as alternative and mutually exclusive oncogenic mechanisms in gastrointestinal stromal tumors (GISTs). This indicates that these mutations contribute to tumor development or progression.

Oncogenic evidence:

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

Predictive, Oncogenic evidence:

Oncogenic: The study discusses how the R481G mutation, along with other PDGFRA mutations, contributes to tumor development as evidenced by the induction of leukemia-like disease in mice when these mutations were introduced into 32D cells. This indicates that the variant plays a role in the pathogenesis of hypereosinophilic syndrome (HES).

Predictive: The abstract mentions that oral imatinib treatment significantly decreased leukemic growth and prolonged survival in mice with PDGFRA mutations, suggesting that the R481G variant is associated with sensitivity to imatinib therapy. This indicates a predictive relationship between the variant and treatment response.

Predictive, Oncogenic evidence:

Oncogenic: The study identifies the Val-561 to Asp mutation in PDGFR alpha as a constitutively activated mutation that induces autonomous proliferation of Ba/F3 cells, indicating its role in tumor development in GISTs without KIT mutations.

Predictive: The results show that the constitutive activation of PDGFR alpha with Val-561 to Asp was effectively inhibited by Imatinib mesylate, suggesting that this variant correlates with sensitivity to this specific therapy.

Oncogenic, Functional evidence:

Oncogenic: The study discusses the H1047R variant as an activating cancer-linked somatic mutation that displays transforming activities in cell culture and has been shown to initiate tumorigenesis in transgenic mouse models, indicating its role in tumor development and progression.

Functional: The abstract mentions that both the H1047R and H1047L mutants show increased basal kinase activities and lipid binding, which suggests that these variants alter the molecular function of the p110alpha protein.

Predictive, Oncogenic evidence:

Oncogenic: The abstract discusses how PIK3CA mutations occur almost exclusively in invasive tumors and suggests that these mutations contribute to tumor development by augmenting earlier activation of the PI3K pathway, indicating a role in tumor progression.

Predictive: The abstract mentions that selective inhibition of the alpha isoform of p110 is an attractive therapeutic strategy for late-stage tumors with co-occurring mutations, suggesting that the presence of PIK3CA mutations may correlate with response to specific therapies targeting this pathway.

Diagnostic, Prognostic, Functional evidence:

Diagnostic: The study discusses the frequency of ALK mutations, including R1275, in neuroblastoma tumors, indicating their association with specific genomic and clinical parameters. This suggests that these mutations can be used to classify or define the disease and its subtypes.

Prognostic: The abstract mentions that the presence of certain mutations, including R1275Q, is correlated with poor survival outcomes, indicating that these variants have prognostic significance independent of therapy.

Functional: The abstract states that the R1275Q mutant is characterized by a different degree of autophosphorylation and transforming capacity compared to the F1174L mutant, indicating that this variant alters molecular function.

Predictive, Oncogenic evidence:

Oncogenic: The F1174L mutation is described as having "more potent transforming activity in vivo," indicating its role in tumor development and progression, which aligns with the definition of an oncogenic variant.

Predictive: The F1174L variant is noted to be "responsible for innate and acquired resistance to crizotinib," suggesting that it correlates with treatment response or resistance, which fits the predictive evidence type.

Oncogenic, Functional evidence:

Oncogenic: The study demonstrates that mutations in the ALK gene contribute to tumor development and progression in neuroblastoma, as evidenced by the ability of the mutated kinases to transform NIH3T3 fibroblasts and form tumors in nude mice.

Functional: The abstract indicates that the mutated ALK kinases displayed increased kinase activity compared to the wild-type kinase, suggesting that these mutations alter the molecular function of the protein.

Diagnostic, Prognostic evidence:

Diagnostic: The study mentions the identification of JAK2 V617F in myeloproliferative neoplasias, indicating its role in classifying or confirming the presence of this specific disease subtype.

Prognostic: The abstract discusses the unfavorable prognostic factor associated with IDH1 mutation status in AML, suggesting that similar considerations could apply to JAK2 V617F in the context of myeloproliferative neoplasias, although this is not explicitly stated for JAK2 V617F.

Oncogenic, Functional evidence:

Oncogenic: The abstract discusses that heterozygous somatic mutations in IDH1, including R132H, occur frequently in gliomas and secondary glioblastomas, suggesting that these mutations contribute to tumor development. The presence of these mutations is linked to the dual effects of loss of normal enzyme function and gain-of-function, which are critical for tumorigenesis.

Functional: The abstract mentions that mutations in IDH1, such as R132H, cause loss of normal enzyme function and gain-of-function, leading to the accumulation of D-2-hydroxyglutarate. This indicates that the variant alters the biochemical function of the enzyme, impacting its activity and the metabolic pathways involved.

Functional evidence:

Functional: The study discusses how glutamine is converted to glutamate and further metabolized to alpha-KG, indicating that this biochemical pathway is altered in cells with mutant IDH1. The inhibition of glutaminase and its effects on glutamate and alpha-KG levels demonstrate a change in molecular function related to this variant.

Diagnostic, Prognostic evidence:

Diagnostic: The abstract mentions that mutations in IDH1 were found in a large fraction of young patients and in most patients with secondary GBMs, indicating its role in classifying and defining a subtype of glioblastoma multiforme.

Prognostic: The abstract states that mutations in IDH1 were associated with an increase in overall survival, suggesting that this variant correlates with disease outcome independent of therapy.

Predictive evidence:

Predictive: The abstract indicates that patients with genomic alterations, including mutations, are more likely to respond to targeted therapeutic agents, suggesting a correlation between the variant and treatment response. This aligns with the definition of predictive evidence, as it discusses the relationship between the variant and therapy effectiveness.

Oncogenic evidence:

Oncogenic: The abstract discusses how the deletion of LKB1 affects tumorigenesis and cancer progression, indicating that this somatic variant contributes to tumor development. The mention of its impact on metastasis and cell adhesion further supports its role in oncogenic processes.

Functional evidence:

Functional: The abstract discusses the role of LKB1 and AMPK in regulating various cellular processes, including metabolism and gene transcription, indicating that the variant may alter molecular or biochemical functions related to these pathways.

Diagnostic, Oncogenic evidence:

Diagnostic: The abstract states that LKB1 is causally linked to Peutz-Jeghers syndrome and is one of the most commonly mutated genes in several cancers, indicating its role in defining and classifying disease subtypes.

Oncogenic: The abstract describes LKB1 as a tumor suppressor gene and mentions its involvement in several cancers, suggesting that mutations in LKB1 contribute to tumor development or progression.

Predisposing, Functional evidence:

Predisposing: The abstract states that "mutations in the LKB1 tumour suppressor threonine kinase cause the inherited Peutz-Jeghers cancer syndrome," indicating that these mutations are germline and confer inherited risk for developing this specific disease.

Functional: The abstract discusses how LKB1 interacts with STRAD and MO25, and how this interaction is crucial for its activation and regulation, demonstrating that the variant alters molecular function through its binding properties and activation mechanisms.

Predictive, Prognostic evidence:

Prognostic: The abstract states that "Expression of mutant p53 correlates with poor prognosis in many tumors," indicating that the presence of the mutant variant is associated with disease outcome independent of therapy.

Predictive: The abstract discusses strategies aimed at reactivation of mutant p53 to provide benefits for treatment of tumors resistant to chemotherapy and radiotherapy, suggesting that the variant correlates with response to specific therapies.

Predictive, Prognostic evidence:

Prognostic: The abstract indicates that Ki-ras mutations might affect the survival rate of colorectal cancer (CRC) patients, suggesting a correlation between these mutations and disease outcome. Additionally, it mentions that different types of TP53 mutations could influence the prognosis of patients based on tumor site, further supporting the prognostic nature of these variants.

Predictive: The abstract also discusses the predictive value of TP53 mutations for survival benefit from 5FU chemotherapy, indicating that specific mutations may correlate with treatment response in CRC patients. This suggests that the presence of certain TP53 mutations can influence the effectiveness of a particular therapy.

nan evidence:

Missing abstract

Oncogenic, Functional evidence:

Oncogenic: The study identifies the AKT1 G49A (E17K) and G145A (E49K) mutations as contributing to tumor development in bladder cancer, demonstrating their transforming activity in NIH3T3 cells, which supports their role as oncogenic variants.

Functional: The abstract mentions that the G49A (E17K) and G145A (E49K) mutations enhance AKT activation, indicating that these variants alter the molecular function of the AKT1 protein, which is a key aspect of their functional impact in cancer.

Predictive, Oncogenic evidence:

Oncogenic: The abstract discusses the Akt1 (e17k) mutant as being unstable and sensitive to functional inhibition, indicating that this somatic variant contributes to tumor development or progression through its role in Akt signaling and response to treatment with SC66.

Predictive: The study highlights that the Akt1 (e17k) mutant is intrinsically sensitive to the functional inhibition by SC66, suggesting a correlation between this variant and the response to a specific therapy, which is indicative of predictive evidence.

Predictive, Oncogenic evidence:

Oncogenic: The study demonstrates that mutations at the PH-KD interface of AKT1 lead to constitutive activation of the protein, contributing to oncogenic signaling, which indicates that these somatic variants play a role in tumor development or progression.

Predictive: The findings suggest that the AKT1 somatic mutants are not effectively inhibited by allosteric AKT inhibitors, indicating a potential resistance to therapy, which correlates with the variant's impact on treatment response.

Prognostic, Functional evidence:

Prognostic: The study reports that patients with tumors harboring the mutant KRas-Gly12Cys variant had worse progression-free survival compared to those with other mutant KRas proteins or wild-type KRas, indicating that this variant correlates with disease outcome independent of therapy.

Functional: The results indicate that the KRas-Gly12Cys variant leads to altered downstream signaling pathways, specifically showing activated Ral signaling and decreased growth factor-dependent Akt activation, which suggests a change in molecular function due to this variant.

Oncogenic evidence:

Oncogenic: The study discusses mutations in the N-ras gene found in patients with cutaneous melanoma, indicating that these mutations contribute to tumor development, particularly in the context of UV damage, which is a known factor in melanoma progression.

Oncogenic evidence:

Oncogenic: The study discusses mutations in the N-ras gene found in patients with cutaneous melanoma, suggesting that these mutations contribute to tumor development, particularly in the context of UV exposure. The mention of mutations being localized at dipyrimidine sites known to be targets of UV damage further supports the notion of these mutations playing a role in tumor progression.

Predictive, Diagnostic evidence:

Diagnostic: The study investigates the incidence of BRAF and NRAS mutations in various melanoma subtypes, indicating that these mutations are associated with specific types of melanoma, particularly in mucosal melanomas. This suggests that the presence of these mutations can help classify or define the disease subtype.

Predictive: The abstract mentions the potential for new therapeutic options of anti-RAF treatment for patients with BRAF mutations in cutaneous melanomas, implying that the presence of the BRAF mutation may correlate with response to this specific therapy.

Predictive, Diagnostic, Oncogenic evidence:

Diagnostic: The study investigates the incidence of BRAF and NRAS mutations in various melanoma subtypes, indicating that these mutations are used to classify and define the molecular genetic profiles of different melanoma types, particularly in mucosal melanomas.

Predictive: The mention of "possible new therapeutic options of anti-RAF treatment" for patients with BRAF mutations suggests that these mutations may correlate with response to specific therapies, indicating a predictive relationship.

Oncogenic: The study discusses the unique oncogenetic pathways of tumor development in different melanoma subtypes, implying that BRAF mutations contribute to tumor development in the context of melanoma, which supports the classification as oncogenic.

Prognostic evidence:

Prognostic: The study indicates that K-ras mutations correlate with disease recurrence, with a significantly higher prevalence in patients with recurrent disease compared to those who are disease-free, suggesting that these mutations serve as a prognostic factor for disease outcome in colorectal carcinoma.

Oncogenic evidence:

Oncogenic: The abstract states that mutations in the ras genes convert them into active oncogenes, indicating that these somatic variants contribute to tumor development or progression. Additionally, the mention of the high incidence of ras mutations in various tumor types supports their role in oncogenesis.

Diagnostic, Prognostic, Oncogenic evidence:

Diagnostic: The study discusses the association of KRAS mutations with various pathological features in sporadic colorectal cancer, indicating that these mutations are used to classify and understand tumor progression and metastasis in this specific disease context.

Prognostic: The presence of KRAS mutations is correlated with advanced disease features such as wall invasion and the presence of lymph node and distant metastases, suggesting that these mutations may provide information about disease outcome independent of therapy.

Oncogenic: The findings indicate that KRAS mutations contribute to the progression of microsatellite-stable colorectal cancer, demonstrating a role in tumor development and progression.

Oncogenic evidence:

Oncogenic: The study demonstrates that mutations at codon 61 of the human rasH gene lead to increased transforming activity, indicating that these somatic variants contribute to tumor development or progression. The significant variation in transforming potency among the mutants further supports their role in oncogenesis.

Predictive, Diagnostic evidence:

Predictive: The abstract discusses the need for mutation screening to optimize patient selection for treatment with EGFR-targeted therapies, indicating that the presence of specific K-Ras mutations, including Arg164Gln, may correlate with treatment response.

Diagnostic: The abstract mentions the identification of mutations outside previously described hotspot codons, suggesting that these mutations, including Arg164Gln, should be considered in the context of colorectal tumors, which implies a role in defining or classifying the disease.

Oncogenic evidence:

Oncogenic: The abstract states that the N-Ras(G60E) mutation, along with other Ras mutants, exhibited oncogenic properties in biochemical and functional assays, indicating that this variant contributes to tumor development or progression.

Oncogenic evidence:

Oncogenic: The abstract states that the N-Ras(G60E) variant, along with other Ras mutants, exhibited oncogenic properties in biochemical and functional assays, indicating its contribution to tumor development or progression.

Predictive, Diagnostic evidence:

Predictive: The study discusses the efficacy of panitumumab in patients with wild-type KRAS tumors, indicating that the presence of this variant correlates with a better response to therapy, as evidenced by prolonged progression-free survival when combined with chemotherapy. The mention of "wild-type rather than mutant KRAS tumours" highlights the predictive nature of the variant in determining treatment outcomes.

Diagnostic: The abstract states that panitumumab is indicated for use in patients with "wild-type rather than mutant KRAS tumours," which implies that the KRAS variant is used to classify patients for treatment eligibility, thus serving a diagnostic purpose in identifying the appropriate patient population for therapy.

nan evidence:

Missing abstract

Diagnostic, Oncogenic, Functional evidence:

Diagnostic: The study discusses the frequency of p53 mutations in different types of brain tumors, indicating that these mutations are associated with specific tumor subtypes, such as anaplastic astrocytoma and glioblastoma multiforme. This suggests that the presence of these mutations can help classify and define the disease.

Oncogenic: The abstract states that the inactivation of PTEN is associated with glioma progression and confirms its role as a tumor suppressor gene, indicating that PTEN mutations contribute to tumor development. The mention of loss of heterozygosity and the inactivation of both PTEN alleles further supports its oncogenic role in high-grade gliomas.

Functional: The study reports that all detected PTEN missense mutations and an in-frame small deletion inactivated PTEN phosphoinositide phosphatase activity in vitro, demonstrating that these variants alter the molecular function of the PTEN protein.

Functional evidence:

Functional: The study demonstrates that the majority of PTEN missense mutations significantly reduce or eliminate phosphatase activity, indicating that these variants alter the molecular function of the PTEN protein. This is supported by the experimental assays conducted to assess the dephosphorylation capabilities of the mutant proteins.

Predictive, Oncogenic evidence:

Predictive: The study discusses how the BRAF V600E mutation is associated with resistance to BRAF inhibitors and explores the response of BRAF V600E mutated melanoma cells to new compounds (NBDHEX and MC3181), indicating a correlation between the variant and treatment response.

Oncogenic: The BRAF V600E mutation is implicated in the development of melanoma, as the study focuses on its role in tumor progression and resistance mechanisms, demonstrating its contribution to cancer biology.

Prognostic, Oncogenic evidence:

Oncogenic: The study identifies the KRAS(G13D) mutation as an oncogenic mutation found in mycosis fungoides and pleomorphic CTCL, indicating its contribution to tumor development in these malignancies.

Prognostic: The presence of the KRAS(G13D) mutation in stage IV patients correlates with significantly decreased overall survival compared to stage IV patients without mutations, suggesting its role as a prognostic marker in CTCL.

Predictive, Oncogenic evidence:

Oncogenic: The study discusses the coexpression of BRAFV600E in human melanoma cells, indicating that this somatic variant contributes to tumor development and progression, particularly in the context of its interaction with NRASQ61R.

Predictive: The results suggest that the presence of BRAFV600E increases susceptibility to cytotoxicity by T cells, indicating a potential predictive relationship regarding treatment response in melanoma patients harboring this variant.

Prognostic evidence:

Prognostic: The study identifies NRAS mutations as being independently associated with decreased overall survival in patients with stage IV melanoma, indicating that the presence of this variant correlates with a poorer disease outcome. The median survival for patients with NRAS mutations was significantly shorter compared to wild-type patients, supporting its role as a prognostic marker.

Oncogenic evidence:

Oncogenic: The study indicates that the variant, which involves a single nucleotide change substituting lysine for glutamine in position 61 of the N-ras gene, is associated with transforming activity in neuroblastoma cells, suggesting that this somatic variant contributes to tumor development.

Oncogenic evidence:

Oncogenic: The study demonstrates that NRAS mutations in codon 12 or 61 are present in acute myelocytic leukemias (AML) and contribute to tumor development, as evidenced by DNA transfection analyses and tumorigenicity assays. This indicates that these somatic mutations play a role in the progression of myeloid malignancies.

Oncogenic evidence:

Oncogenic: The study discusses NRAS mutations, specifically the glycine to aspartic acid substitution at codon 12, in the context of acute myeloid leukemia (AML) and indicates that these mutations are involved in the neoplastic transformation process, suggesting their role in tumor development. The mention of focus-formation assays further supports the oncogenic nature of these mutations.

Predictive evidence:

Predictive: The abstract discusses how the T315I variant is associated with decreased sensitivity to imatinib and highlights the need for alternative therapies, indicating that this variant correlates with resistance to treatment. The mention of "imatinib-resistant mutants" and the comparative potency of other inhibitors against T315I supports its classification as predictive evidence.

Predictive, Prognostic evidence:

Predictive: The study indicates that the detection of BCR-ABL kinase domain mutations is strongly associated with imatinib resistance, suggesting that these mutations can predict treatment response in chronic myeloid leukemia patients. The mention of "acquired resistance" and the correlation with mutation detection supports this classification.

Prognostic: The results highlight that patients with mutations in the adenosine triphosphate (ATP) binding loop (P-loop) had a median survival of only 4.5 months after mutation detection, indicating that these mutations correlate with poor prognosis independent of therapy. This suggests that the presence of these mutations can serve as a prognostic indicator for patient outcomes.