[Paper-level Aggregated] PMCID: PMC3383766

Evidence Type(s): Functional

Summary: Mutation: S184L | Summary: The S184L mutation in MAP2K4 alters molecular function, likely affecting splicing and kinase pathway activation.

Evidence Type: Functional Mutation: M294K | Summary: The M294K mutation in GATA3 is associated with functional inactivation, as indicated by the presence of truncation events and other mutations in the gene.

Evidence Type: Functional Mutation: C77F | Summary: The C77F mutation in AKT1 alters molecular function.

Evidence Type: Functional Mutation: S11F | Summary: The S11F mutation in AKT2 affects molecular function.

Evidence Type: Functional Mutation: S375F | Summary: The S375F mutation in RPS6KB1 alters biochemical function.

Gene→Variant (gene-first): ARID4B(51742):S184L GATA3(2625):M294K AKT1(207):C77F AKT2(208):S11F FOXA1(3169):S375F

Genes: ARID4B(51742) GATA3(2625) AKT1(207) AKT2(208) FOXA1(3169)

Variants: S184L M294K C77F S11F S375F

[Paper-level Aggregated] PMCID: PMC3383766

Evidence Type(s): Oncogenic

Summary: Mutation: G168E | Summary: The G168E mutation in RUNX1 is implicated in tumor development and progression, particularly in the M2 subtype of AML.

Evidence Type: Oncogenic Mutation: R166Q | Summary: The R166Q mutation in RUNX1 contributes to tumor development and is associated with the M2 subtype of AML.

Evidence Type: Oncogenic Mutation: R169K | Summary: The R169K mutation in RUNX1 is involved in tumor progression and is relevant to the M2 subtype of AML.

Evidence Type: Oncogenic Mutation: K700E | Summary: The K700E mutation in SF3B1 is implicated in tumor development and is associated with myelodysplastic syndromes (MDS) and chronic lymphocytic leukemia (CLL).

Evidence Type: Oncogenic Mutation: K666Q | Summary: The K666Q mutation in SF3B1 contributes to tumor development and is relevant in the context of MDS and CLL.

Evidence Type: Oncogenic Mutation: R251H | Summary: The R251H mutation in AGTR2 is associated with angiotensin signaling, which intersects with pathways implicated in tissue fibrosis, suggesting a role in tumor development or progression.

Evidence Type: Oncogenic Mutation: V184I | Summary: The V184I mutation in AGTR2 is linked to angiotensin signaling, indicating its potential contribution to tumor development or progression.

Evidence Type: Oncogenic Mutation: M294K | Summary: The recurrent M294K mutation in GATA3 suggests a role in tumor development, reinforcing the conclusion that GATA3 acts as a tumor suppressor.

Evidence Type: Oncogenic Mutation: V777L | Summary: The V777L mutation in ERBB2 is associated with tumor development, particularly in the context of gefitinib-activating mutations in lung cancer.

Evidence Type: Oncogenic Mutation: A829V | Summary: The A829V mutation in DDR1 is implicated in tumor development and progression.

Evidence Type: Oncogenic Mutation: R611C | Summary: The R611C mutation in DDR1 contributes to tumor development.

Evidence Type: Oncogenic Mutation: E583D | Summary: The E583D mutation in DDR2 is associated with oncogenic activity.

Evidence Type: Oncogenic Mutation: D735H | Summary: The D735H mutation in CSF1R is linked to tumor progression.

Evidence Type: Oncogenic Mutation: M875L | Summary: The M875L mutation in CSF1R contributes to tumor development.

Evidence Type: Oncogenic Mutation: E924K | Summary: The E924K mutation in PDGFRA is associated with oncogenic behavior.

Gene→Variant (gene-first): KMT2B(9757):G168E RUNX1(861):R166Q CYP19A1(1588):R169K SF3B1(23451):K700E SF3B1(23451):K666Q AGTR2(186):R251H AGTR2(186):V184I GATA3(2625):M294K ERBB2(2064):V777L DDR1(780):A829V DDR1(780):R611C NRG1(3084):E583D ARNT(405):D735H PDGFRA(5156):M875L EPHB2(2048):E924K

Genes: KMT2B(9757) RUNX1(861) CYP19A1(1588) SF3B1(23451) AGTR2(186) GATA3(2625) ERBB2(2064) DDR1(780) NRG1(3084) ARNT(405) PDGFRA(5156) EPHB2(2048)

Variants: G168E R166Q R169K K700E K666Q R251H V184I M294K V777L A829V R611C E583D D735H M875L E924K

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

Evidence Type(s): Oncogenic, Functional

Summary: Evidence Type: Oncogenic | Mutation: V777L | Summary: The V777L mutation in ERBB2 is associated with tumor development, particularly in the context of gefitinib-activating mutations in lung cancer. Evidence Type: Oncogenic | Mutation: A829V | Summary: The A829V mutation in DDR1 is implicated in tumor development and progression. Evidence Type: Oncogenic | Mutation: R611C | Summary: The R611C mutation in DDR1 contributes to tumor development. Evidence Type: Oncogenic | Mutation: E583D | Summary: The E583D mutation in DDR2 is associated with oncogenic activity. Evidence Type: Oncogenic | Mutation: D735H | Summary: The D735H mutation in CSF1R is linked to tumor progression. Evidence Type: Oncogenic | Mutation: M875L | Summary: The M875L mutation in CSF1R contributes to tumor development. Evidence Type: Oncogenic | Mutation: E924K | Summary: The E924K mutation in PDGFRA is associated with oncogenic behavior. Evidence Type: Functional | Mutation: C77F | Summary: The C77F mutation in AKT1 alters molecular function. Evidence Type: Functional | Mutation: S11F | Summary: The S11F mutation in AKT2 affects molecular function. Evidence Type: Functional | Mutation: S375F | Summary: The S375F mutation in RPS6KB1 alters biochemical function.

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

Summary: Evidence Type: Functional | Mutation: M294K | Summary: The M294K mutation in GATA3 is associated with functional inactivation, as indicated by the presence of truncation events and other mutations in the gene. Evidence Type: Oncogenic | Mutation: M294K | Summary: The recurrent M294K mutation in GATA3 suggests a role in tumor development, reinforcing the conclusion that GATA3 acts 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): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: R251H | Summary: The R251H mutation in AGTR2 is associated with angiotensin signaling, which intersects with pathways implicated in tissue fibrosis, suggesting a role in tumor development or progression. Evidence Type: Oncogenic | Mutation: V184I | Summary: The V184I mutation in AGTR2 is linked to angiotensin signaling, indicating its potential contribution to tumor development or progression.

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

Summary: Evidence Type: Oncogenic | Mutation: G168E | Summary: The G168E mutation in RUNX1 is implicated in tumor development and progression, particularly in the M2 subtype of AML. Evidence Type: Oncogenic | Mutation: R166Q | Summary: The R166Q mutation in RUNX1 contributes to tumor development and is associated with the M2 subtype of AML. Evidence Type: Oncogenic | Mutation: R169K | Summary: The R169K mutation in RUNX1 is involved in tumor progression and is relevant to the M2 subtype of AML. Evidence Type: Oncogenic | Mutation: K700E | Summary: The K700E mutation in SF3B1 is implicated in tumor development and is associated with myelodysplastic syndromes (MDS) and chronic lymphocytic leukemia (CLL). Evidence Type: Oncogenic | Mutation: K666Q | Summary: The K666Q mutation in SF3B1 contributes to tumor development and is relevant in the context of MDS and CLL. Evidence Type: Functional | Mutation: S184L | Summary: The S184L mutation in MAP2K4 alters molecular function, likely affecting splicing and kinase pathway activation.

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

[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