[Paper-level Aggregated] PMCID: PMC10690049

Evidence Type(s): Oncogenic

Summary: Mutation: G12C | Summary: The KRAS G12C mutation contributes to tumor development and progression, as indicated by its presence in various cancer cell lines and the observed effects of targeted therapies.

Evidence Type: Oncogenic Mutation: G12D | Summary: The KRAS G12D mutation is associated with tumor development or progression, as it is mentioned in the context of MEFs that are used to study cancer behavior.

Gene→Variant (gene-first): KRAS(3845):G12C KRAS(3845):G12D

Genes: KRAS(3845)

Variants: G12C G12D

[Paper-level Aggregated] PMCID: PMC10690049

Evidence Type(s): Predictive

Summary: Mutation: G12C | Summary: The KRAS G12C mutation is associated with sensitivity to specific therapies, demonstrated by the synergistic inhibition of cell proliferation in KRAS G12C-mutant cell lines treated with MRTX849/AMG510 and KPT9274.

Evidence Type: Predictive Mutation: G12D | Summary: The KRAS G12D mutation was tested in the context of a drug combination, indicating a potential correlation with resistance to therapy, as the KRAS G12D MEFs were refractory to growth inhibition.

Gene→Variant (gene-first): KRAS(3845):G12C KRAS(3845):G12D

Genes: KRAS(3845)

Variants: G12C G12D

[Paragraph-level] PMCID: PMC10690049 Section: RESULTS PassageIndex: 7

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G12D | Summary: The KRASG12D mutation was tested in the context of a drug combination, indicating a potential correlation with resistance to therapy, as the KRASG12D MEFs were refractory to growth inhibition. Evidence Type: Oncogenic | Mutation: G12D | Summary: The KRASG12D mutation is associated with tumor development or progression, as it is mentioned in the context of MEFs that are used to study cancer behavior.

Gene→Variant (gene-first): 3845:G12D

Genes: 3845

Variants: G12D

[Paragraph-level] PMCID: PMC10690049 Section: RESULTS PassageIndex: 6

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: G12C | Summary: The KRAS G12C mutation is associated with sensitivity to specific therapies, as demonstrated by the synergistic inhibition of cell proliferation in KRAS G12C-mutant cell lines when treated with MRTX849/AMG510 and KPT9274. Evidence Type: Oncogenic | Mutation: G12C | Summary: The KRAS G12C mutation contributes to tumor development and progression, as indicated by its presence in various cancer cell lines and the observed effects of targeted therapies.

Gene→Variant (gene-first): 3845:G12C

Genes: 3845

Variants: G12C

[Paper-level Aggregated] PMCID: PMC10690049

Evidence Type(s): Oncogenic, Predictive, Functional

Justification: Oncogenic: The text discusses the KRAS G12C and G12D mutations in the context of cancer cell lines, indicating that these variants are associated with tumorigenic properties, particularly highlighting the specific response of KRASG12C to treatment. Predictive: The evidence suggests that the presence of the KRAS G12C mutation predicts a positive response to the drug combination of MRTX849 and KPT9274, as indicated by the synergistic growth inhibition observed in KRASG12C-mutant cell lines. Functional: The study demonstrates the functional impact of KRAS G12C and G12D mutations on cell growth and drug response, showing that KRASG12C-mutant cells are sensitive to specific inhibitors while KRASG12D-mutant cells are not.

Gene→Variant (gene-first): KRAS(3845):G12C KRAS(3845):G12D

Genes: KRAS(3845)

Variants: G12C G12D

[Paragraph-level] PMCID: PMC10690049 Section: RESULTS PassageIndex: 7

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the response of KRASG12D mutant MEFs to a drug combination, indicating that the variant is associated with resistance to growth inhibition by the therapies tested. Oncogenic: The KRASG12D variant is implicated in tumor behavior, as it is described in the context of MEFs (mouse embryonic fibroblasts) and their growth characteristics, suggesting a role in tumor development or progression.

Gene→Variant (gene-first): 3845:G12D

Genes: 3845

Variants: G12D

[Paragraph-level] PMCID: PMC10690049 Section: RESULTS PassageIndex: 6

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the response of KRAS G12C-mutant cells to specific therapies, indicating a correlation between the variant and sensitivity to the drugs MRTX849/AMG510 and KPT9274. Oncogenic: The variant KRAS G12C is implicated in tumor development, as the passage describes its presence in cancer cell lines and their proliferation in response to treatment, suggesting a role in cancer progression.

Gene→Variant (gene-first): 3845:G12C

Genes: 3845

Variants: G12C

[Paragraph-level] PMCID: PMC10690049 Section: RESULTS PassageIndex: 7

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the response of KRASG12D mutant MEFs to a drug combination, indicating that the variant is associated with resistance to growth inhibition by the therapies tested. Oncogenic: The KRASG12D variant is implicated in tumor behavior, as it is described in the context of MEFs (mouse embryonic fibroblasts) and their growth characteristics, suggesting a role in tumor development or progression.

Gene→Variant (gene-first): 3845:G12D

Genes: 3845

Variants: G12D

[Paragraph-level] PMCID: PMC10690049 Section: RESULTS PassageIndex: 6

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the response of KRAS G12C-mutant cells to specific therapies, indicating a correlation between the variant and sensitivity to the drugs MRTX849/AMG510 and KPT9274. Oncogenic: The variant KRAS G12C is implicated in tumor development, as the passage describes its presence in cancer cell lines and their proliferation in response to treatment, suggesting a role in cancer progression.

Gene→Variant (gene-first): 3845:G12C

Genes: 3845

Variants: G12C