Survival of patients with structurally-groupedTP53mutations in ovarian and breast cancers

// Brandon-Luke L. Seagle 1 , Kevin H. Eng 2 , Monica Dandapani 1 , Judy Y. Yeh 1 , Kunle Odunsi 3 , Shohreh Shahabi 4 1 Department of Obstetrics, Gynecology and Reproductive Sciences, Western Connecticut Health Network, Danbury, CT, USA 2 Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, USA 3 Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA 4 Division 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.