Oncotarget

Research Papers:

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

Brandon-Luke L. Seagle _, Kevin H. Eng, Monica Dandapani, Judy Y. Yeh, Kunle Odunsi and Shohreh Shahabi

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Oncotarget. 2015; 6:18641-18652. https://doi.org/10.18632/oncotarget.4080

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Abstract

Brandon-Luke L. Seagle1, Kevin H. Eng2, Monica Dandapani1, Judy Y. Yeh1, Kunle Odunsi3, Shohreh Shahabi4

1Department of Obstetrics, Gynecology and Reproductive Sciences, Western Connecticut Health Network, Danbury, CT, USA

2Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, USA

3Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA

4Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Prentice Women’s Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

Correspondence to:

Shohreh Shahabi, e-mail: sshahabi@nm.org

Keywords: ovarian neoplasms, breast neoplasms, TP53 gene, mutation, biological markers

Received: March 07, 2015     Accepted: June 12, 2015     Published: June 22, 2015

ABSTRACT

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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