[Paper-level Aggregated] PMCID: PMC4999563

Evidence Type(s): Prognostic, Oncogenic, Functional

Justification: Prognostic: The text indicates that mutations in KRAS, particularly the G12C and G13D variants, are associated with inferior overall survival (OS) and progression-free survival (PFS) in metastatic colorectal cancer patients compared to non-mutated tumors. Oncogenic: The presence of KRAS mutations, including G12C and G13D, is linked to poor survival outcomes, suggesting that these mutations contribute to the oncogenic process in colorectal cancer. Functional: The analysis of various KRAS mutations, including A146T, Q61H, and others, indicates that these variants were evaluated for their impact on efficacy endpoints, suggesting a functional role in tumor behavior and treatment response.

Gene→Variant (gene-first): KRAS(3845):A146T KRAS(3845):G12C KRAS(3845):G12D KRAS(3845):G13D KRAS(3845):Q61H KRAS(3845):G12V BRAF(673):V600E

Genes: KRAS(3845) BRAF(673)

Variants: A146T G12C G12D G13D Q61H G12V V600E

[Paragraph-level] PMCID: PMC4999563 Section: RESULTS PassageIndex: 11

Evidence Type(s): Prognostic, Oncogenic

Justification: Prognostic: The passage discusses the correlation of KRAS exon 2 variants, specifically G12C and G13D, with overall survival (OS) and progression-free survival (PFS), indicating their impact on disease outcome independent of therapy. Oncogenic: The mention of KRAS exon 2 variants suggests their role in tumor development or progression, as they are associated with inferior survival outcomes in patients with mutated tumors compared to non-mutated tumors.

Gene→Variant (gene-first): 3845:G12C 3845:G12D 3845:G12V 3845:G13D

Genes: 3845

Variants: G12C G12D G12V G13D

[Paragraph-level] PMCID: PMC4999563 Section: RESULTS PassageIndex: 10

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses the median progression-free survival (PFS) and overall survival (OS) associated with specific KRAS mutations, indicating a correlation with disease outcomes independent of therapy. Diagnostic: The mention of KRAS exon 2 mutant tumor subtypes suggests that these variants are used to classify or define a specific disease subtype.

Gene→Variant (gene-first): 3845:A146T 3845:G12C 3845:G12D 3845:G13D 3845:Q61H

Genes: 3845

Variants: A146T G12C G12D G13D Q61H

[Paragraph-level] PMCID: PMC4999563 Section: RESULTS PassageIndex: 4

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage indicates that tumors carrying BRAF V600E mutations were identified, suggesting an association with the classification of the tumors. Oncogenic: The mention of BRAF V600E mutations in tumors implies a role in tumor development or progression, characteristic of oncogenic variants.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC4999563 Section: ABSTRACT PassageIndex: 9

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage indicates that KRAS G12C and G13D mutations are associated with inferior progression-free survival (PFS) and overall survival (OS) in mCRC patients, suggesting a correlation with disease outcome independent of therapy. Diagnostic: The mention of KRAS mutations being associated with heterogeneous outcomes compared to unmutated tumors implies that these variants can be used to classify or define a disease subtype in mCRC.

Gene→Variant (gene-first): 3845:G12C 3845:G13D

Genes: 3845

Variants: G12C G13D

[Paragraph-level] PMCID: PMC4999563 Section: ABSTRACT PassageIndex: 7

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses the correlation of KRAS mutations, including specific variants like G12C and G13D, with inferior overall survival (OS) and progression-free survival (PFS), indicating their impact on disease outcome independent of therapy. Diagnostic: The passage mentions that mutations in KRAS were diagnosed in tumors, indicating that these mutations are used to classify or define the disease.

Gene→Variant (gene-first): 3845:G12C 3845:G12D 3845:G12V 3845:G13D

Genes: 3845

Variants: G12C G12D G12V G13D

[Paragraph-level] PMCID: PMC4999563 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses how KRAS G12C and G13D mutations correlate with inferior progression-free and overall survival in metastatic colorectal cancer patients, indicating their prognostic significance. Diagnostic: The mention of KRAS mutations being associated with tumor characteristics suggests their role in classifying or defining the disease subtype in colorectal cancer.

Gene→Variant (gene-first): 3845:G12C 3845:G13D

Genes: 3845

Variants: G12C G13D

[Paragraph-level] PMCID: PMC4999563 Section: RESULTS PassageIndex: 11

Evidence Type(s): Prognostic, Oncogenic

Justification: Prognostic: The passage discusses the correlation of KRAS exon 2 variants, specifically G12C and G13D, with overall survival (OS) and progression-free survival (PFS), indicating their impact on disease outcome independent of therapy. Oncogenic: The mention of KRAS exon 2 variants suggests their role in tumor development or progression, as they are associated with inferior survival outcomes in patients with mutated tumors compared to non-mutated tumors.

Gene→Variant (gene-first): 3845:G12C 3845:G12D 3845:G12V 3845:G13D

Genes: 3845

Variants: G12C G12D G12V G13D

[Paragraph-level] PMCID: PMC4999563 Section: RESULTS PassageIndex: 10

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses the median progression-free survival (PFS) and overall survival (OS) associated with specific KRAS mutations, indicating a correlation with disease outcomes independent of therapy. Diagnostic: The mention of KRAS exon 2 mutant tumor subtypes suggests that these variants are used to classify or define a specific disease subtype.

Gene→Variant (gene-first): 3845:A146T 3845:G12C 3845:G12D 3845:G13D 3845:Q61H

Genes: 3845

Variants: A146T G12C G12D G13D Q61H

[Paragraph-level] PMCID: PMC4999563 Section: RESULTS PassageIndex: 4

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage indicates that tumors carrying BRAF V600E mutations were identified, suggesting an association with the classification of the tumors. Oncogenic: The mention of BRAF V600E mutations in tumors implies a role in tumor development or progression, characteristic of oncogenic variants.

Gene→Variant (gene-first): 673:V600E

Genes: 673

Variants: V600E

[Paragraph-level] PMCID: PMC4999563 Section: ABSTRACT PassageIndex: 9

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage indicates that KRAS G12C and G13D mutations are associated with inferior progression-free survival (PFS) and overall survival (OS) in mCRC patients, suggesting a correlation with disease outcome independent of therapy. Diagnostic: The mention of KRAS mutations being associated with heterogeneous outcomes compared to unmutated tumors implies that these variants can be used to classify or define a disease subtype in mCRC.

Gene→Variant (gene-first): 3845:G12C 3845:G13D

Genes: 3845

Variants: G12C G13D

[Paragraph-level] PMCID: PMC4999563 Section: ABSTRACT PassageIndex: 7

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses the correlation of KRAS mutations, including specific variants like G12C and G13D, with inferior overall survival (OS) and progression-free survival (PFS), indicating their impact on disease outcome independent of therapy. Diagnostic: The passage mentions that mutations in KRAS were diagnosed in tumors, indicating that these mutations are used to classify or define the disease.

Gene→Variant (gene-first): 3845:G12C 3845:G12D 3845:G12V 3845:G13D

Genes: 3845

Variants: G12C G12D G12V G13D

[Paragraph-level] PMCID: PMC4999563 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Prognostic, Diagnostic

Justification: Prognostic: The passage discusses how KRAS G12C and G13D mutations correlate with inferior progression-free and overall survival in metastatic colorectal cancer patients, indicating their prognostic significance. Diagnostic: The mention of KRAS mutations being associated with tumor characteristics suggests their role in classifying or defining the disease subtype in colorectal cancer.

Gene→Variant (gene-first): 3845:G12C 3845:G13D

Genes: 3845

Variants: G12C G13D