Abstract 3889: Genomic landscape of gynecologic cancers with poor prognosis in Japan, an analysis of the national database of comprehensive genomic profiling tests

Abstract Objective: Comprehensive genomic profiling (CGP) tests were approved in Japan in June 2019 under universal health insurance coverage for cancer patients who have finished (or almost finished) standardized treatment. All the data are collected to the “Center for Cancer Genomics and Advanced Therapeutics (C-CAT) ” under written informed consent. Up to date, over 60, 000 CGP data have been deposited with a 99. 7% consent rate. This study aims to analyze mutational landscape of gynecologic cancers, especially with poor prognosis, by using this database. Methods: We analyzed CGP datasets from 3, 006 gynecologic cancer patients using FoundationOne® CDx (F1CDx), the most commonly tested in Japan. This study was ethically approved by our institutional ethics committee (#2021341G) and the Information Utilization Review Board of C-CAT (#CDU2022-026N). Results: Endometrial cancers (n=561) showed high rates of tumor mutational burden-high (TMB-H) (13. 9%) and MSI-high (MSI-H) (10. 8%), especially in endometrioid carcinomas. POLE exonuclease mutations were less frequent (1. 4%) compared to TCGA data (7%), while TP53 mutations were more common (54. 4% vs. 29% in TCGA), suggesting the impact of prognosis of the molecular subtypes. Other frequently mutated genes included PIK3CA (41%), PTEN (35%), ARID1A (31%) and KRAS (26%). In 839 cervical cancers, TMB-H prevalence was 14. 2%, with low MSI-H at 1. 5%. TMB-H was significantly higher in squamous cell carcinomas (20. 6%) than adenocarcinomas (8. 3%). Frequent mutations included PIK3CA (32%), STK11 (20%), TP53 (20%), KRAS (14%), and CDKN2A (11%). TP53 mutations were significantly higher than TCGA data (5%), particularly in mucinous carcinomas (60%), indicating a prevalence of HPV-independent tumors with poorer prognosis. Actionable mutations were generally more frequent in adenocarcinomas than in squamous cell carcinomas, including KRAS (32. 2%), TP53 (29. 4%), CDKN2A (18. 3%), and ERBB2 (16. 7%). In 1, 606 ovarian cancers, the ratio of TMB-H was 5. 0%, and MSI-H was 1. 2%. TMB-H rates varied between 3. 3-6. 5% across histological types, while the ratio of MSI-H was significantly lower in serous carcinomas (0. 3%) than non-serous carcinomas. Pathogenic mutations in the POLE exonuclease domain were rare in cervical (0. 0%) and ovarian (0. 2%) cancers. Conclusion: The C-CAT database offers insights into the mutational landscape of various cancers and histological subtypes, especially those with poor prognosis, highlighting the unmet needs for drug development in these gynecologic cancers. Citation Format: Qian Xi, Hidenori Kage, Miho Ogawa, Asami Matsunaga, Akira Nishijima, Kenbun Sone, Kei Kawana, Katsutoshi Oda. Genomic landscape of gynecologic cancers with poor prognosis in Japan, an analysis of the national database of comprehensive genomic profiling tests abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 3889.