[Paper-level Aggregated] PMCID: PMC6280667

Evidence Type(s): Predictive

Summary: Mutation: TP53 | Summary: TP53 mutations were shown to cause a broad pattern of drug resistance, with some drugs trending more sensitive to TP53 mutant cases, indicating a correlation with treatment response.

Evidence Type: Predictive Mutation: ASXL1 | Summary: ASXL1 mutations were associated with drug resistance, but also showed sensitivity to specific drugs, suggesting a predictive role in treatment response.

Evidence Type: Predictive Mutation: NRAS | Summary: NRAS mutations correlated largely with resistance to most drugs, but also showed predicted sensitivity to MAPK inhibitors, indicating a potential predictive value for therapy.

Evidence Type: Predictive Mutation: KRAS | Summary: KRAS mutations were associated with resistance to most drugs, while also showing sensitivity to MAPK inhibitors, suggesting a predictive role in treatment response.

Evidence Type: Predictive Mutation: IDH2 | Summary: IDH2 mutations conferred sensitivity to a broad spectrum of drugs, indicating a predictive association with treatment response.

Evidence Type: Predictive Mutation: IDH1 | Summary: IDH1 mutations were associated with resistance to most drugs, suggesting a predictive role in treatment response.

Evidence Type: Predictive Mutation: RUNX1 | Summary: RUNX1 mutations correlated with sensitivity to PIK3C/MTOR inhibitors, indicating a predictive association with treatment response.

Evidence Type: Predictive Mutation: FLT3 | Summary: FLT3 mutations exhibited a significant pattern of co-occurrence with sensitivity to the FDA approved drug, ibrutinib, indicating a predictive role in treatment response.

Evidence Type: Predictive Mutation: NPM1 | Summary: NPM1 mutations were significantly more sensitive to ibrutinib compared to wild type, suggesting a predictive association with treatment response.

Evidence Type: Predictive Mutation: BCOR | Summary: BCOR mutations showed sensitivity to alternative drugs, indicating a predictive role in treatment response, particularly in specific combinatorial mutation settings.

Gene→Variant (gene-first): NA:TP53 NA:ASXL1 NA:NRAS NA:KRAS NA:IDH2 NA:IDH1 NA:RUNX1 NA:FLT3 NA:NPM1 NA:BCOR

Genes: NA

Variants: TP53 ASXL1 NRAS KRAS IDH2 IDH1 RUNX1 FLT3 NPM1 BCOR

[Paragraph-level] PMCID: PMC6280667 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive

Summary: Evidence Type: Predictive | Mutation: TP53 | Summary: TP53 mutations were shown to cause a broad pattern of drug resistance, with some drugs trending more sensitive to TP53 mutant cases, indicating a correlation with treatment response. Evidence Type: Predictive | Mutation: ASXL1 | Summary: ASXL1 mutations were associated with drug resistance, but also showed sensitivity to specific drugs, suggesting a predictive role in treatment response. Evidence Type: Predictive | Mutation: NRAS | Summary: NRAS mutations correlated largely with resistance to most drugs, but also showed predicted sensitivity to MAPK inhibitors, indicating a potential predictive value for therapy. Evidence Type: Predictive | Mutation: KRAS | Summary: KRAS mutations were associated with resistance to most drugs, while also showing sensitivity to MAPK inhibitors, suggesting a predictive role in treatment response. Evidence Type: Predictive | Mutation: IDH2 | Summary: IDH2 mutations conferred sensitivity to a broad spectrum of drugs, indicating a predictive association with treatment response. Evidence Type: Predictive | Mutation: IDH1 | Summary: IDH1 mutations were associated with resistance to most drugs, suggesting a predictive role in treatment response. Evidence Type: Predictive | Mutation: RUNX1 | Summary: RUNX1 mutations correlated with sensitivity to PIK3C/MTOR inhibitors, indicating a predictive association with treatment response. Evidence Type: Predictive | Mutation: FLT3 | Summary: FLT3 mutations exhibited a significant pattern of co-occurrence with sensitivity to the FDA approved drug, ibrutinib, indicating a predictive role in treatment response. Evidence Type: Predictive | Mutation: NPM1 | Summary: NPM1 mutations were significantly more sensitive to ibrutinib compared to wild type, suggesting a predictive association with treatment response. Evidence Type: Predictive | Mutation: BCOR | Summary: BCOR mutations showed sensitivity to alternative drugs, indicating a predictive role in treatment response, particularly in specific combinatorial mutation settings.

Gene→Variant (gene-first): 8233:serine/arginine

Genes: 8233

Variants: serine/arginine

[Paper-level Aggregated] PMCID: PMC6280667

Evidence Type(s): Functional, Prognostic

Justification: Functional: The text discusses the correlation of mutations in splicesome components, including serine/arginine rich 2 (ZRSR2), with novel sensitivity to several drugs, indicating a functional role of these mutations in drug response. Prognostic: The mention of mutations in TP53 and ASXL1 as causing a broad pattern of drug resistance suggests that these mutations are associated with poor prognostic features in AML cases.

Gene→Variant (gene-first): ZRSR2(8233):serine/arginine

Genes: ZRSR2(8233)

Variants: serine/arginine

[Paragraph-level] PMCID: PMC6280667 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive

Justification: Predictive: The passage discusses the correlation of mutations, including those in splicing components like ZRSR2, with sensitivity to various drugs, indicating a relationship between the variant and treatment response.

Gene→Variant (gene-first): 8233:serine/arginine

Genes: 8233

Variants: serine/arginine

[Paragraph-level] PMCID: PMC6280667 Section: RESULTS PassageIndex: 9

Evidence Type(s): Predictive

Justification: Predictive: The passage discusses the correlation of mutations, including those in splicing components like ZRSR2, with sensitivity to various drugs, indicating a relationship between the variant and treatment response.

Gene→Variant (gene-first): 8233:serine/arginine

Genes: 8233

Variants: serine/arginine