[Paper-level Aggregated] PMCID: PMC3973211

Evidence Type(s): Prognostic, Oncogenic, Functional

Justification: Prognostic: The text indicates that mutations on Arg248 and Arg282 residues are associated with significantly shorter overall survival times in cancer patients, as demonstrated by Kaplan-Meier survival analysis and multivariate Cox regression analysis. Oncogenic: The passage discusses how p53 mutations, particularly R248 and R282, confer novel oncogenic functions and are linked to increased expression of drug metabolism enzymes, suggesting a role in cancer progression and treatment resistance. Functional: The evidence shows that p53 mutations R248W and R282W induce higher expression of the CYP3A4 enzyme, which is involved in drug metabolism, indicating a functional impact of these mutations on cellular processes related to chemotherapy response.

Gene→Variant (gene-first): TP53(7157):Arg248 TP53(7157):Arg282 TP53(7157):G245 TP53(7157):R175 TP53(7157):R248 TP53(7157):R249S TP53(7157):R273 TP53(7157):R282 TP53(7157):Y220 TP53(7157):R282W TP53(7157):R175H TP53(7157):R248W TP53(7157):R273H TP53(7157):R248Q/W

Genes: TP53(7157)

Variants: Arg248 Arg282 G245 R175 R248 R249S R273 R282 Y220 R282W R175H R248W R273H R248Q/W

[Paragraph-level] PMCID: PMC3973211 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Prognostic, Predictive, Oncogenic

Justification: Prognostic: The passage indicates that mutations at Arg248 and Arg282 positions are associated with shorter patient survival, suggesting a correlation with disease outcome independent of therapy. Predictive: The passage discusses the association of p53 mutations with resistance to several CYP3A4-metabolized chemotherapeutic drugs, indicating a correlation with treatment response. Oncogenic: The mention of p53 mutations contributing to gain of novel oncogenic functions and their association with cancer cell lines suggests that these somatic variants play a role in tumor development or progression.

Gene→Variant (gene-first): 7157:Arg248 7157:Arg282 7157:R282W

Genes: 7157

Variants: Arg248 Arg282 R282W

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the relationship between p53 mutations (including R175H, R248W, R273H, R282W) and resistance to chemotherapy, specifically noting that cells with these mutations showed higher viability and increased IC50 for various drugs, indicating a correlation with drug resistance. Oncogenic: The passage implies that the p53 mutations contribute to tumor behavior by affecting cell response to chemotherapy, suggesting their role in tumor development or progression.

Gene→Variant (gene-first): 7157:R175H 7157:R248W 7157:R273H 7157:R282W

Genes: 7157

Variants: R175H R248W R273H R282W

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 10

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the association between p53 mutations (R248, R282) and the expression of CYP3A4, a drug metabolism enzyme, indicating a correlation with drug clearance and potential response to chemotherapeutic drugs. Functional: The passage describes how p53 mutations (R248, R282) alter the expression levels of the CYP3A4 enzyme, demonstrating a change in molecular function related to drug metabolism.

Gene→Variant (gene-first): 7157:R175 7157:R175H 7157:R248 7157:R248W 7157:R273 7157:R273H 7157:R282 7157:R282W

Genes: 7157

Variants: R175 R175H R248 R248W R273 R273H R282 R282W

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 8

Evidence Type(s): Prognostic, Functional

Justification: Prognostic: The passage mentions that R248Q/W and R282W are associated with mortality, indicating a correlation with disease outcome. Functional: The passage discusses the enrichment of specific gene sets linked to cellular respiration and drug metabolism enzymes for certain mutations, suggesting alterations in molecular function.

Gene→Variant (gene-first): 7157:R175H 7157:R248Q/W 7157:R248W 7157:R273H 7157:R282W

Genes: 7157

Variants: R175H R248Q/W R248W R273H R282W

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 7

Evidence Type(s): Diagnostic, Predictive

Justification: Diagnostic: The passage indicates that the R282 mutation is associated with drug metabolism enzymes, suggesting its role in defining or classifying a specific biological context related to drug metabolism. Predictive: The mention of the R282 mutation in relation to drug metabolism enzymes implies a potential correlation with response or sensitivity to therapies that involve these enzymes.

Gene→Variant (gene-first): 7157:R282

Genes: 7157

Variants: R282

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 6

Evidence Type(s): Prognostic, Oncogenic

Justification: Prognostic: The passage discusses the association of R248 and R282 mutations with shorter patient survival, indicating a correlation with disease outcome independent of therapy. Oncogenic: The mention of mice carrying the humanized mutation on R248 exhibiting significantly shorter survival time suggests that this somatic variant contributes to tumor development or progression.

Gene→Variant (gene-first): 7157:R175 7157:R248 7157:R273 7157:R282

Genes: 7157

Variants: R175 R248 R273 R282

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 4

Evidence Type(s): Prognostic, Oncogenic

Justification: Prognostic: The passage discusses how mutations at Arg248 and Arg282 correlate with significantly shorter overall survival times, indicating a relationship between these variants and disease outcome independent of therapy. Oncogenic: The mention of p53 mutations, including those at Arg248 and Arg282, suggests a role in tumor development or progression, as these mutations are associated with survival outcomes in cancer patients.

Gene→Variant (gene-first): 7157:Arg248 7157:Arg282 7157:G245 7157:R175 7157:R248 7157:R249S 7157:R273 7157:R282 7157:Y220

Genes: 7157

Variants: Arg248 Arg282 G245 R175 R248 R249S R273 R282 Y220

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 2

Evidence Type(s): Prognostic

Justification: Prognostic: The passage indicates that mutations at Arg282 and Arg248 are associated with shorter patient survival, which correlates with disease outcome independent of therapy.

Gene→Variant (gene-first): 7157:Arg248 7157:Arg282

Genes: 7157

Variants: Arg248 Arg282

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 12

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the relationship between p53 mutations (including R175H, R248W, R273H, R282W) and resistance to chemotherapy, specifically noting that cells with these mutations showed higher viability and increased IC50 for various drugs, indicating a correlation with drug resistance. Oncogenic: The passage implies that the p53 mutations contribute to tumor behavior by affecting cell response to chemotherapy, suggesting their role in tumor development or progression.

Gene→Variant (gene-first): 7157:R175H 7157:R248W 7157:R273H 7157:R282W

Genes: 7157

Variants: R175H R248W R273H R282W

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 10

Evidence Type(s): Predictive, Functional

Justification: Predictive: The passage discusses the association between p53 mutations (R248, R282) and the expression of CYP3A4, a drug metabolism enzyme, indicating a correlation with drug clearance and potential response to chemotherapeutic drugs. Functional: The passage describes how p53 mutations (R248, R282) alter the expression levels of the CYP3A4 enzyme, demonstrating a change in molecular function related to drug metabolism.

Gene→Variant (gene-first): 7157:R175 7157:R175H 7157:R248 7157:R248W 7157:R273 7157:R273H 7157:R282 7157:R282W

Genes: 7157

Variants: R175 R175H R248 R248W R273 R273H R282 R282W

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 8

Evidence Type(s): Prognostic, Functional

Justification: Prognostic: The passage mentions that R248Q/W and R282W are associated with mortality, indicating a correlation with disease outcome. Functional: The passage discusses the enrichment of specific gene sets linked to cellular respiration and drug metabolism enzymes for certain mutations, suggesting alterations in molecular function.

Gene→Variant (gene-first): 7157:R175H 7157:R248Q/W 7157:R248W 7157:R273H 7157:R282W

Genes: 7157

Variants: R175H R248Q/W R248W R273H R282W

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 7

Evidence Type(s): Diagnostic, Predictive

Justification: Diagnostic: The passage indicates that the R282 mutation is associated with drug metabolism enzymes, suggesting its role in defining or classifying a specific biological context related to drug metabolism. Predictive: The mention of the R282 mutation in relation to drug metabolism enzymes implies a potential correlation with response or sensitivity to therapies that involve these enzymes.

Gene→Variant (gene-first): 7157:R282

Genes: 7157

Variants: R282

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 6

Evidence Type(s): Prognostic, Oncogenic

Justification: Prognostic: The passage discusses the association of R248 and R282 mutations with shorter patient survival, indicating a correlation with disease outcome independent of therapy. Oncogenic: The mention of mice carrying the humanized mutation on R248 exhibiting significantly shorter survival time suggests that this somatic variant contributes to tumor development or progression.

Gene→Variant (gene-first): 7157:R175 7157:R248 7157:R273 7157:R282

Genes: 7157

Variants: R175 R248 R273 R282

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 4

Evidence Type(s): Prognostic, Oncogenic

Justification: Prognostic: The passage discusses how mutations at Arg248 and Arg282 correlate with significantly shorter overall survival times, indicating a relationship between these variants and disease outcome independent of therapy. Oncogenic: The mention of p53 mutations, including those at Arg248 and Arg282, suggests a role in tumor development or progression, as these mutations are associated with survival outcomes in cancer patients.

Gene→Variant (gene-first): 7157:Arg248 7157:Arg282 7157:G245 7157:R175 7157:R248 7157:R249S 7157:R273 7157:R282 7157:Y220

Genes: 7157

Variants: Arg248 Arg282 G245 R175 R248 R249S R273 R282 Y220

[Paragraph-level] PMCID: PMC3973211 Section: RESULTS PassageIndex: 2

Evidence Type(s): Prognostic

Justification: Prognostic: The passage indicates that mutations at Arg282 and Arg248 are associated with shorter patient survival, which correlates with disease outcome independent of therapy.

Gene→Variant (gene-first): 7157:Arg248 7157:Arg282

Genes: 7157

Variants: Arg248 Arg282