期刊
ONCOTARGET
卷 6, 期 21, 页码 18641-18652出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.4080
关键词
ovarian neoplasms; breast neoplasms; TP53 gene; mutation; biological markers
资金
- Roswell Park Cancer Institute Alliance Foundation Award
- National Cancer Institute Cancer Center [NIH 2P30 CA016056-36, NIH 1R01CA158318-01A1]
- RPCI-UPCI Ovarian Cancer SPORE [NIH P50CA159981-01A1, K01LM012100, P30CA016056]
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.
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