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

• Published in: Gynecologic oncology Vol. 159; no. 2; pp. 381 - 386
• Main Authors: Wallbillich, John J., Morris, Robert T., Ali-Fehmi, Rouba
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2020
• Subjects: Adult; Aged; Aged, 80 and over; BRCA1 Protein; BRCA2 Protein; Cystadenocarcinoma, Serous - genetics; Female; Germ-Line Mutation; High-Throughput Nucleotide Sequencing; Homologous Recombination; Humans; Middle Aged; Mutation Rate; Ovarian Neoplasms - genetics; Uterine Neoplasms - genetics
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2020.08.012

To compare the frequencies of somatic homologous recombination (HR) gene mutations identified in next-generation sequencing (NGS) genomic profiling of uterine serous carcinomas (USCs) and high-grade serous ovarian carcinomas (HGSOCs). 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 genes were queried for each group with respect to mutation frequency. For each HR gene, the difference in mutation frequency between the two groups was evaluated using Fisher's exact test. The threshold for statistical significance was p-value < .05. In the USC group, there were 457 samples from 451 patients. In the HGSOC group, there were 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-BRCA HR 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. Somatic HR gene mutations were commonly identified in NGS genomic profiling of USC. Mutation frequencies for non-BRCA HR genes were 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. •Somatic HR gene mutations were frequent in patients with USC who underwent clinical-grade NGS tumor profiling.•Somatic mutation rates for non-BRCA HR genes were not significantly different between USC and HGSOC.•These findings suggest testing and targeting somatic HR deficiency could be beneficial for women with USC.