[Paper-level Aggregated] PMCID: PMC3383766

Evidence Type(s): Oncogenic, Functional, Predictive, Prognostic

Justification: Oncogenic: The text describes multiple mutations in genes associated with cancer, including those in druggable tyrosine kinase domains, indicating their potential role in oncogenesis. Functional: The identification of mutations leading to functional inactivation of MAP3K1 and MAP2K4 suggests that these mutations affect the normal function of these genes, which are involved in critical signaling pathways. Predictive: The mention of mutations in druggable tyrosine kinase domains implies that these mutations may predict response to targeted therapies, as they are associated with specific cancer treatments. Prognostic: The correlation of mutation frequencies with clinical outcomes, such as the association of CDH1 mutations with lobular breast cancer, suggests that these mutations may have prognostic implications.

Gene→Variant (gene-first): DDR1(780):A829V AKT1(207):C77F ARNT(405):D735H NRG1(3084):E583D EPHB2(2048):E924K PDGFRA(5156):M875L DDR1(780):R611C AKT2(208):S11F FOXA1(3169):S375F ERBB2(2064):V777L KMT2B(9757):G168E SF3B1(23451):K666Q SF3B1(23451):K700E MAP3K4(4216):N104S RUNX1(861):R166Q CYP19A1(1588):R169K ARID4B(51742):S184L GATA3(2625):M294K AGTR2(186):R251H AGTR2(186):V184I

Genes: DDR1(780) AKT1(207) ARNT(405) NRG1(3084) EPHB2(2048) PDGFRA(5156) AKT2(208) FOXA1(3169) ERBB2(2064) KMT2B(9757) SF3B1(23451) MAP3K4(4216) RUNX1(861) CYP19A1(1588) ARID4B(51742) GATA3(2625) AGTR2(186)

Variants: A829V C77F D735H E583D E924K M875L R611C S11F S375F V777L G168E K666Q K700E N104S R166Q R169K S184L M294K R251H V184I

[Paragraph-level] PMCID: PMC3383766 Section: RESULTS PassageIndex: 21

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses mutations in specific genes that are associated with druggable tyrosine kinase domains, indicating their relevance in defining or classifying disease subtypes. Oncogenic: The mention of mutations in tyrosine kinase domains suggests that these variants may contribute to tumor development or progression, particularly in the context of cancer-related mutations.

Gene→Variant (gene-first): 780:A829V 207:C77F 405:D735H 3084:E583D 2048:E924K 5156:M875L 780:R611C 208:S11F 3169:S375F 2064:V777L

Genes: 780 207 405 3084 2048 5156 208 3169 2064

Variants: A829V C77F D735H E583D E924K M875L R611C S11F S375F V777L

[Paragraph-level] PMCID: PMC3383766 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage indicates that the M294K mutation in GATA3 is one of several mutations that include truncation events, suggesting a role in functional inactivation of the protein. Oncogenic: The mention of M294K as a recurrent mutation in tumors suggests that it may contribute to tumor development or progression, particularly in the context of GATA3 being identified as a tumor suppressor.

Gene→Variant (gene-first): 2625:M294K

Genes: 2625

Variants: M294K

[Paragraph-level] PMCID: PMC3383766 Section: RESULTS PassageIndex: 8

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage mentions that AGTR2 harbored two missense mutations (V184I and R251H) and describes AGTR2 as a gene associated with familial hypercholesterolemia, indicating its role in defining or classifying a disease. Oncogenic: The passage discusses mutations in AGTR2 and their potential involvement in angiotensin signaling and tissue fibrosis, which are relevant to tumor development or progression, suggesting a role in oncogenesis.

Gene→Variant (gene-first): 186:R251H 186:V184I

Genes: 186

Variants: R251H V184I

[Paragraph-level] PMCID: PMC3383766 Section: RESULTS PassageIndex: 7

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses mutations in RUNX1, which is implicated in the M2 subtype of AML, indicating that these somatic variants contribute to tumor development or progression. Functional: The passage mentions that mutations in RUNX1 affect its role as a transcription factor, which suggests that these variants alter molecular or biochemical function.

Gene→Variant (gene-first): 9757:G168E 23451:K666Q 23451:K700E 4216:N104S 861:R166Q 1588:R169K 51742:S184L

Genes: 9757 23451 4216 861 1588 51742

Variants: G168E K666Q K700E N104S R166Q R169K S184L

[Paragraph-level] PMCID: PMC3383766 Section: RESULTS PassageIndex: 21

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage discusses mutations in specific genes that are associated with druggable tyrosine kinase domains, indicating their relevance in defining or classifying disease subtypes. Oncogenic: The mention of mutations in tyrosine kinase domains suggests that these variants may contribute to tumor development or progression, particularly in the context of cancer-related mutations.

Gene→Variant (gene-first): 780:A829V 207:C77F 405:D735H 3084:E583D 2048:E924K 5156:M875L 780:R611C 208:S11F 3169:S375F 2064:V777L

Genes: 780 207 405 3084 2048 5156 208 3169 2064

Variants: A829V C77F D735H E583D E924K M875L R611C S11F S375F V777L

[Paragraph-level] PMCID: PMC3383766 Section: RESULTS PassageIndex: 10

Evidence Type(s): Functional, Oncogenic

Justification: Functional: The passage indicates that the M294K mutation in GATA3 is one of several mutations that include truncation events, suggesting a role in functional inactivation of the protein. Oncogenic: The mention of M294K as a recurrent mutation in tumors suggests that it may contribute to tumor development or progression, particularly in the context of GATA3 being identified as a tumor suppressor.

Gene→Variant (gene-first): 2625:M294K

Genes: 2625

Variants: M294K

[Paragraph-level] PMCID: PMC3383766 Section: RESULTS PassageIndex: 8

Evidence Type(s): Diagnostic, Oncogenic

Justification: Diagnostic: The passage mentions that AGTR2 harbored two missense mutations (V184I and R251H) and describes AGTR2 as a gene associated with familial hypercholesterolemia, indicating its role in defining or classifying a disease. Oncogenic: The passage discusses mutations in AGTR2 and their potential involvement in angiotensin signaling and tissue fibrosis, which are relevant to tumor development or progression, suggesting a role in oncogenesis.

Gene→Variant (gene-first): 186:R251H 186:V184I

Genes: 186

Variants: R251H V184I

[Paragraph-level] PMCID: PMC3383766 Section: RESULTS PassageIndex: 7

Evidence Type(s): Oncogenic, Functional

Justification: Oncogenic: The passage discusses mutations in RUNX1, which is implicated in the M2 subtype of AML, indicating that these somatic variants contribute to tumor development or progression. Functional: The passage mentions that mutations in RUNX1 affect its role as a transcription factor, which suggests that these variants alter molecular or biochemical function.

Gene→Variant (gene-first): 9757:G168E 23451:K666Q 23451:K700E 4216:N104S 861:R166Q 1588:R169K 51742:S184L

Genes: 9757 23451 4216 861 1588 51742

Variants: G168E K666Q K700E N104S R166Q R169K S184L