Survival of patients with structurally-grouped TP53 mutations in ovarian and breast cancers

被引：22

作者：

Seagle, Brandon-Luke L. ^{[1
]}

Eng, Kevin H. ^{[2
]}

Dandapani, Monica ^{[1
]}

Yeh, Judy Y. ^{[1
]}

Odunsi, Kunle ^{[3
]}

Shahabi, Shohreh ^{[4
]}

机构：

[1] Western Connecticut Hlth Network, Dept Obstet Gynecol & Reprod Sci, Danbury, CT USA

[2] Roswell Pk Canc Inst, Dept Biostat & Bioinformat, Buffalo, NY 14263 USA

[3] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA

[4] Northwestern Univ, Prentice Womens Hosp, Feinburg Sch Med, Div Gynecol Oncol,Dept Obstet & Gynecol, Chicago, IL 60611 USA

来源：

ONCOTARGET | 2015年 / 6卷 / 21期

关键词：

ovarian neoplasms; breast neoplasms; TP53; gene; mutation; biological markers; GENE-MUTATIONS; POOR SURVIVAL; P53;

D O I：

10.18632/oncotarget.4080

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The objective of this study was to determine if ovarian cancer patients with a TP53 mutation grouped by location of the mutation within the p53 protein structure exhibit differential survival outcomes. Data from patients with high grade serous ovarian cancer (HGS OvCa) (N = 316) or breast cancer (BrCa) (N = 981) sequenced by The Cancer Genome Atlas (TCGA) was studied by Kaplan-Meier and Cox proportional hazards survival analysis. A TP53 DNA binding domain (BD) missense mutation (MM) occurred in 58.5% (185/316) of HGS OvCas and 16.8% (165/981) of BrCas. Patients with a TP53 DNA BD MM grouped by structural location had significantly different overall survival (OS) and progression free survival (PFS). Median OS (months) of HGS OvCa patients by structural group were: Sheet-loop-helix stabilizers, 31.1; DNA minor groove residue R248, 33.6; Wild-type, 34.2; all other MMs, 44.5; DNA major groove residues, 84.1, and zinc ion coordinating residues, 87.0 (log-rank p = 0.006). PFS of DNA major groove MM cases was longer than TP53 wild-type cases (19.1 versus 10.1 months, log-rank p = 0.038). HGS OvCa and BrCa patients with structurally-grouped TP53 DNA BD MMs have different survival outcomes.

引用

页码：18641 / 18652

页数：12

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