Characterizing TP53 mutations in ovarian carcinomas with and without concurrent BRCA1 or BRCA2 mutations

Area of Science:

• Oncology
• Genetics
• Genomics

Background:

• TP53 gene mutations are frequent in ovarian carcinoma (OC), but their prognostic significance remains debated.
• The interplay between TP53 and BRCA1/BRCA2 (BRCA) mutations in OC outcomes requires clarification.

Purpose of the Study:

• To investigate the association of TP53 mutations with ovarian cancer outcomes.
• To examine the interaction between TP53 and BRCA mutations.
• To compare different TP53 mutation classification schemes.

Main Methods:

• Next-generation sequencing was performed on 393 OC cases.
• TP53 mutations were classified using Structural, Functional, and Hotspot schemes.
• Survival analysis (Kaplan-Meier, Cox regression) and logistic regression for platinum resistance were conducted, adjusting for BRCA status.

Main Results:

• TP53 mutations occurred in 76.8% of the cohort and 87.9% of high-grade serous carcinoma (HGSC).
• TP53 mutation frequency was higher in cases with BRCA mutations (92.3% vs. 72.2%).
• TP53 mutations were not associated with overall survival but were linked to platinum sensitivity (OR 0.41, p=0.048), independent of BRCA status.

Conclusions:

• BRCA mutations frequently co-occur with TP53 mutations in ovarian cancer.
• TP53 mutations are associated with platinum sensitivity in OC, irrespective of BRCA mutation status or classification scheme.