Journal article
Characterizing TP53 mutations in ovarian carcinomas with and without concurrent BRCA1 or BRCA2 mutations
Gynecologic oncology, Vol.160(3), pp.786-792
03/2021
DOI: 10.1016/j.ygyno.2020.12.007
PMCID: PMC8491988
PMID: 33375991
Abstract
Mutations in the TP53 tumor suppressor gene are common in ovarian carcinoma (OC) but their impact on outcomes is controversial. We sought to define the relationship of TP53 mutations to cancer outcomes and their interactions with co-occurrent BRCA1 or BRCA2 (BRCA) mutations, comparing three different TP53 mutation classification schemes.
We performed next generation sequencing on 393 cases of OC prospectively followed for survival. TP53 mutations were classified according to three schemes termed Structural, Functional, and Hotspot. Mutation distribution was compared between cases with and without BRCA mutations. In a subset of 281 cases of high grade serous carcinoma (HGSC), overall survival was compared using Kaplan-Meier curves, logrank testing, and multivariate Cox regression analysis, both stratified and adjusted for BRCA mutation status. Multivariate logistic regression was used to analyze the effects of TP53 mutation type on platinum resistance.
TP53 mutations were identified in 76.8% of the total cohort (n = 302/393) and 87.9% of HGSC (n = 247/281). Cases with BRCA mutations demonstrated significantly higher TP53 mutation frequency overall (n = 84/91, 92.3% vs. n = 218/302, 72.2%, p < 0.001). TP53 mutations were not associated with overall survival, even when stratified by BRCA mutation. TP53 mutations were associated with platinum sensitivity, even after adjusting for BRCA mutation status (OR 0.41, p = 0.048). The choice of TP53 mutation classification scheme was not found to alter any significant outcome.
BRCA mutations significantly co-occur with TP53 mutations. After adjusting for BRCA mutations, TP53 mutations are associated with platinum sensitivity, and this effect is not dependent on TP53 mutation type.
•TP53 mutations were identified in 76.8% of ovarian carcinomas and 87.9% of high grade serous carcinomas in this cohort.•BRCA1 or BRCA2 mutations co-occur with TP53 mutations in ovarian carcinoma.•TP53 mutations are associated with platinum sensitivity, but not overall survival, in high grade serous ovarian carcinoma.
Details
- Title: Subtitle
- Characterizing TP53 mutations in ovarian carcinomas with and without concurrent BRCA1 or BRCA2 mutations
- Creators
- Talayeh S. Ghezelayagh - University of WashingtonKathryn P. Pennington - University of WashingtonBarbara M. Norquist - University of WashingtonNithisha Khasnavis - Fred Hutch Cancer CenterMarc R. Radke - University of WashingtonMark R. Kilgore - University of WashingtonRochelle L. Garcia - University of WashingtonMing Lee - University of WashingtonRonit Katz - University of WashingtonKimberly K. Leslie - University of IowaRosa Ana Risques - University of WashingtonElizabeth M. Swisher - University of Washington
- Resource Type
- Journal article
- Publication Details
- Gynecologic oncology, Vol.160(3), pp.786-792
- DOI
- 10.1016/j.ygyno.2020.12.007
- PMID
- 33375991
- PMCID
- PMC8491988
- NLM abbreviation
- Gynecol Oncol
- ISSN
- 0090-8258
- eISSN
- 1095-6859
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health; DOI: 10.13039/100000005, name: U.S. Department of Defense
- Language
- English
- Date published
- 03/2021
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9984320849802771
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