Comparing mutation frequencies for homologous recombination genes in uterine serous and high-grade serous ovarian carcinomas: A case for homologous recombination deficiency testing in uterine serous carcinoma

Objective. To compare the frequencies of somatic homologous recombination (HR) genemutations identified in next-generation sequencing (NGS) genomic profiling of uterine serous carcinomas (USCs) and high-grade serous ovarian carcinomas (HGSOCs). Methods. Data for this analysis was obtained from AACR Project GENIE, a multi-institutional dataset of clinical-grade NGS genomic profiling results for many cancer sites and histologic subtypes, through cBioPortal. Patient/specimen groups used for analysis were USC and HGSOC. 14 HR geneswere queried for each group with respect tomutation frequency. For each HR gene, the difference in mutation frequency between the two groupswas evaluated using Fisher's exact test. The threshold for statistical significance was p-value < .05. Results. In the USC group, therewere 457 samples from 451 patients. In the HGSOC group, therewere 1537 samples from 1515 patients. The most frequently mutated HR gene for USC was BRCA2 (4.84%) and for HGSOC was BRCA1 (9.07%). Mutation frequency was significantly different between USC and HGSOC for BRCA 1 (p < .001) and BRCA2 (p=.0379). For the 12 non-BRCAHR genes, mutation frequency was not significantly different between USC and HGSOC. The rate of patients with at least one HR gene mutation in their profiled tumor was 16.85% for USC and 25.21% of HGSOC. Most USC patients with a somatic HR mutation had only one HR gene mutated. Conclusions. Somatic HR genemutations were commonly identified in NGS genomic profiling of USC. Mutation frequencies for non-BRCA HR geneswere not significantly different between USC and HGSOC. These data add to the growing rationale for HR deficiency tumor testing and targeting (e.g., with PARP inhibitors) in future clinical trial development for women with USC. (C) 2020 Elsevier Inc. All rights reserved.