[Paper-level Aggregated] PMCID: PMC10011885

Evidence Type(s): Functional

Summary: Mutation: A163G | Summary: The KDR A163G mutation is mentioned in the context of targeted sequencing, suggesting it may alter molecular or biochemical function.

Evidence Type: Functional Mutation: R106H | Summary: The MSH6 R106H mutation is identified in the context of targeted sequencing, indicating a potential alteration in molecular or biochemical function.

Gene→Variant (gene-first): KDR(3791):A163G SLTM(79811):R106H

Genes: KDR(3791) SLTM(79811)

Variants: A163G R106H

[Paper-level Aggregated] PMCID: PMC10011885

Evidence Type(s): Oncogenic

Summary: Mutation: V600E | Summary: The BRAF V600E mutation is associated with tumor development and progression in various cancers, including metastatic colorectal cancer. It contributes to tumor dynamics, is retained during disease progression, and is implicated as an oncogenic driver.

Evidence Type: Oncogenic Mutation: G13C | Summary: The NRAS G13C mutation was detected in a patient, indicating its potential role in tumor development or progression.

Evidence Type: Oncogenic Mutation: Q61H | Summary: The KRAS Q61H mutation is associated with the emergence of subclonal mutations contributing to tumor development and progression, as indicated by its detection prior to disease progression.

Evidence Type: Oncogenic Mutation: Q61L | Summary: The KRAS Q61L mutation is part of multiple subclonal KRAS mutations identified, which are implicated in tumor development and progression.

Evidence Type: Oncogenic Mutation: G12N | Summary: The KRAS G12N mutation is included among the subclonal mutations that contribute to tumor development and progression.

Evidence Type: Oncogenic Mutation: G13D | Summary: The KRAS G13D mutation is identified as a subclonal mutation that plays a role in tumor development and progression.

Evidence Type: Oncogenic Mutation: G12D | Summary: The NRAS G12D mutation is part of the identified mutations that contribute to tumor development and progression.

Gene→Variant (gene-first): BRAF(673):V600E NRAS(4893):G13C KRAS(3845):Q61H NRAS(4893):Q61L KRAS(3845):G12N KRAS(3845):G13D KRAS(3845):G12D

Genes: BRAF(673) NRAS(4893) KRAS(3845)

Variants: V600E G13C Q61H Q61L G12N G13D G12D

[Paper-level Aggregated] PMCID: PMC10011885

Evidence Type(s): Prognostic

Summary: Mutation: V600E | Summary: Higher levels of ctDNA for the BRAF V600E mutation at baseline are associated with inferior progression-free survival (PFS) and overall survival (OS). The mutation correlates with disease outcomes, as patients with higher week 2 and week 4 baseline ratios had inferior PFS and OS, indicating its prognostic significance.

Gene→Variant (gene-first): BRAF(673):V600E

Genes: BRAF(673)

Variants: V600E

[Paper-level Aggregated] PMCID: PMC10011885

Evidence Type(s): Diagnostic

Summary: Mutation: V600E | Summary: The presence of the BRAF V600E mutation is used to classify patients with selected cancers, confirming their mutation-positive status. It is also utilized to define and classify patients based on the presence of mutant ctDNA in plasma, indicating its role in diagnosing the disease.

Gene→Variant (gene-first): BRAF(673):V600E

Genes: BRAF(673)

Variants: V600E

[Paper-level Aggregated] PMCID: PMC10011885

Evidence Type(s): Predictive

Summary: Mutation: V600E | Summary: The BRAF V600E mutation correlates with clinical benefit and treatment response, as patients with lower ctDNA levels achieved better outcomes. It is associated with early changes in ctDNA levels that predict outcomes to combination vemurafenib and erlotinib therapy. Additionally, it serves as a predictor of progression-free survival (PFS) and overall survival (OS) based on week 2 and week 4 baseline ratios of ctDNA levels. The mutation is also linked to the development of combination therapies involving oral BRAF inhibitors and EGFR-targeting antibodies, and it is associated with treatment response to vemurafenib and erlotinib in metastatic colorectal cancer.

Gene→Variant (gene-first): BRAF(673):V600E

Genes: BRAF(673)

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: ABSTRACT PassageIndex: 7

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The BRAF V600E mutation in metastatic colorectal cancer is associated with treatment response to vemurafenib and erlotinib, indicating its predictive value for therapy efficacy. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation is implicated in tumor development and progression in metastatic colorectal cancer, supporting its classification as an oncogenic variant.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: ABSTRACT PassageIndex: 3

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The BRAF V600E mutation is associated with the development of combination therapies involving oral BRAF inhibitors and EGFR-targeting antibodies, indicating its potential role in predicting response to these therapies. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation is implicated in the progression of metastatic colorectal cancer, suggesting its role as an oncogenic driver in tumor development.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 24

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: Q61H | Summary: The KRAS Q61H mutation is associated with the emergence of subclonal mutations contributing to tumor development and progression, as indicated by its detection prior to disease progression. Evidence Type: Oncogenic | Mutation: Q61L | Summary: The KRAS Q61L mutation is part of the multiple subclonal KRAS mutations identified, which are implicated in tumor development and progression. Evidence Type: Oncogenic | Mutation: G12N | Summary: The KRAS G12N mutation is included among the subclonal mutations that contribute to tumor development and progression. Evidence Type: Oncogenic | Mutation: G13D | Summary: The KRAS G13D mutation is identified as a subclonal mutation that plays a role in tumor development and progression. Evidence Type: Oncogenic | Mutation: G12D | Summary: The NRAS G12D mutation is part of the identified mutations that contribute to tumor development and progression. Evidence Type: Functional | Mutation: A163G | Summary: The KDR A163G mutation is mentioned in the context of targeted sequencing, suggesting it may alter molecular or biochemical function. Evidence Type: Functional | Mutation: R106H | Summary: The MSH6 R106H mutation is identified in the context of targeted sequencing, indicating a potential alteration in molecular or biochemical function.

Gene→Variant (gene-first): 3791:A163G 3845:G12D 3845:G12N 3845:G13D 3845:Q61H 4893:Q61L 79811:R106H 673:V600E

Genes: 3791 3845 4893 79811 673

Variants: A163G G12D G12N G13D Q61H Q61L R106H V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 23

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation was retained in patients at disease progression, indicating its role in tumor development or progression.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 20

Evidence Type(s): Predictive, Prognostic

Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The BRAF V600E mutation is assessed as a predictor of progression-free survival (PFS) and overall survival (OS) based on the week 2 and week 4 baseline ratios of ctDNA levels, indicating its correlation with treatment response. Evidence Type: Prognostic | Mutation: V600E | Summary: The BRAF V600E mutation correlates with disease outcomes, as patients with higher week 2 and week 4 baseline ratios had inferior PFS and OS, suggesting its role in predicting survival independent of therapy.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 19

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: V600E | Summary: The BRAF V600E mutation is associated with early changes in ctDNA levels that predict outcomes to combination vemurafenib and erlotinib therapy, indicating its role in treatment response. Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation contributes to tumor development or progression, as indicated by its presence in ctDNA dynamics analyzed in the context of therapy.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 16

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: G13C | Summary: The NRAS G13C mutation was detected in a patient, indicating its potential role in tumor development or progression.

Gene→Variant (gene-first): 4893:G13C

Genes: 4893

Variants: G13C

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 15

Evidence Type(s): Diagnostic, Prognostic, Predictive

Summary: Evidence Type: Diagnostic | Mutation: V600E | Summary: The BRAF V600E mutation is used to define and classify patients based on the presence of mutant ctDNA in plasma, indicating its role in diagnosing the disease. Evidence Type: Prognostic | Mutation: V600E | Summary: Higher levels of ctDNA for the BRAF V600E mutation at baseline are associated with inferior progression-free survival (PFS) and overall survival (OS), indicating its prognostic significance. Evidence Type: Predictive | Mutation: V600E | Summary: The presence of the BRAF V600E mutation correlates with clinical benefit, as patients with lower ctDNA levels achieved better outcomes, suggesting its predictive value for treatment response.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic, Diagnostic

Summary: Evidence Type: Oncogenic | Mutation: V600E | Summary: The BRAF V600E mutation is associated with tumor development or progression in various cancers, including non-colorectal cancers. Evidence Type: Diagnostic | Mutation: V600E | Summary: The presence of the BRAF V600E mutation is used to classify patients with selected cancers, confirming their mutation-positive status.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paper-level Aggregated] PMCID: PMC10011885

Evidence Type(s): Oncogenic, Predictive, Functional

Justification: Oncogenic: The BRAF V600E mutation is identified as a significant alteration in metastatic colorectal cancer (mCRC) and is associated with the disease's progression and treatment resistance, indicating its role in oncogenesis. Predictive: Early ctDNA dynamics, including changes in BRAF V600E levels, were shown to predict treatment efficacy, with significant correlations between ctDNA levels and clinical outcomes such as progression-free survival (PFS) and overall survival (OS). Functional: The emergence of KRAS and NRAS mutations, including specific variants like KRAS Q61H and G13D, was linked to treatment resistance, suggesting that these mutations have functional implications in the context of therapy response.

Gene→Variant (gene-first): KDR(3791):A163G KRAS(3845):G12D KRAS(3845):G12N KRAS(3845):G13D KRAS(3845):Q61H NRAS(4893):Q61L SLTM(79811):R106H BRAF(673):V600E NRAS(4893):G13C

Genes: KDR(3791) KRAS(3845) NRAS(4893) SLTM(79811) BRAF(673)

Variants: A163G G12D G12N G13D Q61H Q61L R106H V600E G13C

[Paragraph-level] PMCID: PMC10011885 Section: ABSTRACT PassageIndex: 7

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the overall response rates and clinical benefit rates of patients with BRAF V600E positive metastatic colorectal cancer treated with vemurafenib and erlotinib, indicating a correlation with treatment response. Oncogenic: The mention of BRAF V600E in the context of metastatic colorectal cancer suggests that this somatic variant contributes to tumor development or progression.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: ABSTRACT PassageIndex: 3

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the use of BRAF V600E mutant colorectal cancer in the context of therapy, specifically mentioning the effectiveness of combination therapy with BRAF inhibitors and EGFR-targeting antibodies, indicating a correlation with treatment response. Oncogenic: The mention of BRAF V600E in the context of metastatic colorectal cancer suggests that this somatic variant contributes to tumor development or progression, as it is associated with a significant clinical problem in this cancer type.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 24

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the emergence of KRAS mutations associated with treatment resistance, indicating a correlation with response to therapy, specifically in the context of chemotherapy and targeted treatments. Oncogenic: The passage describes the identification of KRAS mutations that contribute to tumor progression, particularly noting the emergence of these mutations prior to disease progression, which is indicative of their role in cancer development.

Gene→Variant (gene-first): 3791:A163G 3845:G12D 3845:G12N 3845:G13D 3845:Q61H 4893:Q61L 79811:R106H 673:V600E

Genes: 3791 3845 4893 79811 673

Variants: A163G G12D G12N G13D Q61H Q61L R106H V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 23

Evidence Type(s): Oncogenic

Justification: Oncogenic: The passage discusses the retention of the BRAF V600E mutation in patients with mCRC, indicating its role in tumor development or progression, particularly in the context of disease progression and treatment response.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 20

Evidence Type(s): Prognostic, Predictive

Justification: Prognostic: The passage discusses how the BRAF V600E mutation VAF ratio correlates with progression-free survival (PFS) and overall survival (OS), indicating that it is associated with disease outcomes independent of therapy. Predictive: The assessment of the BRAF V600E mutation VAF ratio as a predictor of PFS and OS suggests that it may correlate with treatment response, indicating its predictive value in the context of therapy.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 19

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses how early changes in ctDNA levels, specifically related to the BRAF V600E variant, are predictive of clinical benefit and objective response to combination vemurafenib and erlotinib therapy. Oncogenic: The BRAF V600E variant is implicated in tumor dynamics and is associated with the response to treatment, indicating its role in tumor development or progression.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 16

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage indicates that the presence of genetic alterations, including the NRAS G13C mutation, correlates with clinical benefit from treatment, suggesting a predictive relationship regarding therapy response. Diagnostic: The mention of the NRAS G13C mutation being detected in a patient implies its role in identifying or classifying the disease, which aligns with diagnostic evidence. Oncogenic: The NRAS G13C mutation is discussed in the context of being a mutation found in a patient, which suggests its potential role in tumor development or progression.

Gene→Variant (gene-first): 4893:G13C

Genes: 4893

Variants: G13C

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 15

Evidence Type(s): Diagnostic, Prognostic, Oncogenic

Justification: Diagnostic: The passage indicates that BRAF V600E mutant ctDNA is detected in a significant proportion of patients, suggesting its use in defining or confirming the presence of a specific disease. Prognostic: The passage states that higher levels of ctDNA at baseline are associated with inferior progression-free survival (PFS) and overall survival (OS), indicating a correlation with disease outcome independent of therapy. Oncogenic: The presence of the BRAF V600E variant in ctDNA suggests its role in tumor development or progression, as it is a known somatic mutation associated with cancer.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 3

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage mentions that the non-colorectal cancer cohort included patients who were BRAF V600E mutation positive, indicating that this variant is used to classify or define a specific group of patients with selected cancers. Oncogenic: The BRAF V600E mutation is associated with tumor development in various cancers, as indicated by its presence in patients with selected cancers, suggesting its role in oncogenesis.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: ABSTRACT PassageIndex: 7

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the overall response rates and clinical benefit rates of patients with BRAF V600E positive metastatic colorectal cancer treated with vemurafenib and erlotinib, indicating a correlation with treatment response. Oncogenic: The mention of BRAF V600E in the context of metastatic colorectal cancer suggests that this somatic variant contributes to tumor development or progression.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: ABSTRACT PassageIndex: 3

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the use of BRAF V600E mutant colorectal cancer in the context of therapy, specifically mentioning the effectiveness of combination therapy with BRAF inhibitors and EGFR-targeting antibodies, indicating a correlation with treatment response. Oncogenic: The mention of BRAF V600E in the context of metastatic colorectal cancer suggests that this somatic variant contributes to tumor development or progression, as it is associated with a significant clinical problem in this cancer type.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 24

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the emergence of KRAS mutations associated with treatment resistance, indicating a correlation with response to therapy, specifically in the context of chemotherapy and targeted treatments. Oncogenic: The passage describes the identification of KRAS mutations that contribute to tumor progression, particularly noting the emergence of these mutations prior to disease progression, which is indicative of their role in cancer development.

Gene→Variant (gene-first): 3791:A163G 3845:G12D 3845:G12N 3845:G13D 3845:Q61H 4893:Q61L 79811:R106H 673:V600E

Genes: 3791 3845 4893 79811 673

Variants: A163G G12D G12N G13D Q61H Q61L R106H V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 23

Evidence Type(s): Oncogenic

Justification: Oncogenic: The passage discusses the retention of the BRAF V600E mutation in patients with mCRC, indicating its role in tumor development or progression, particularly in the context of disease progression and treatment response.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 20

Evidence Type(s): Prognostic, Predictive

Justification: Prognostic: The passage discusses how the BRAF V600E mutation VAF ratio correlates with progression-free survival (PFS) and overall survival (OS), indicating that it is associated with disease outcomes independent of therapy. Predictive: The assessment of the BRAF V600E mutation VAF ratio as a predictor of PFS and OS suggests that it may correlate with treatment response, indicating its predictive value in the context of therapy.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 19

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses how early changes in ctDNA levels, specifically related to the BRAF V600E variant, are predictive of clinical benefit and objective response to combination vemurafenib and erlotinib therapy. Oncogenic: The BRAF V600E variant is implicated in tumor dynamics and is associated with the response to treatment, indicating its role in tumor development or progression.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 16

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage indicates that the presence of genetic alterations, including the NRAS G13C mutation, correlates with clinical benefit from treatment, suggesting a predictive relationship regarding therapy response. Diagnostic: The mention of the NRAS G13C mutation being detected in a patient implies its role in identifying or classifying the disease, which aligns with diagnostic evidence. Oncogenic: The NRAS G13C mutation is discussed in the context of being a mutation found in a patient, which suggests its potential role in tumor development or progression.

Gene→Variant (gene-first): 4893:G13C

Genes: 4893

Variants: G13C

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 15

Evidence Type(s): Diagnostic, Prognostic, Oncogenic

Justification: Diagnostic: The passage indicates that BRAF V600E mutant ctDNA is detected in a significant proportion of patients, suggesting its use in defining or confirming the presence of a specific disease. Prognostic: The passage states that higher levels of ctDNA at baseline are associated with inferior progression-free survival (PFS) and overall survival (OS), indicating a correlation with disease outcome independent of therapy. Oncogenic: The presence of the BRAF V600E variant in ctDNA suggests its role in tumor development or progression, as it is a known somatic mutation associated with cancer.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC10011885 Section: RESULTS PassageIndex: 3

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage mentions that the non-colorectal cancer cohort included patients who were BRAF V600E mutation positive, indicating that this variant is used to classify or define a specific group of patients with selected cancers. Oncogenic: The BRAF V600E mutation is associated with tumor development in various cancers, as indicated by its presence in patients with selected cancers, suggesting its role in oncogenesis.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E