title: Survival of patients with structurally-grouped TP53 mutations in ovarian and breast cancers.
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.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Western Connecticut Health Network, Danbury, CT, USA.
authors.forename: Brandon-Luke L
authors.initials: BL
authors.lastname: Seagle
authors.affiliation: Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Kevin H
authors.initials: KH
authors.lastname: Eng
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Western Connecticut Health Network, Danbury, CT, USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Dandapani
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Western Connecticut Health Network, Danbury, CT, USA.
authors.forename: Judy Y
authors.initials: JY
authors.lastname: Yeh
authors.affiliation: Department of Gynecologic Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Kunle
authors.initials: K
authors.lastname: Odunsi
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Prentice Women's Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Shohreh
authors.initials: S
authors.lastname: Shahabi
mesh_terms: D000368:Aged; D001665:Binding Sites / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D015331:Cohort Studies; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D008958:Models, Molecular; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D016016:Proportional Hazards Models; D017434:Protein Structure, Tertiary; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53
keywords: TP53 gene; biological markers; breast neoplasms; mutation; ovarian neoplasms