Abstract 6606: Genomic features of histological and molecular subtypes in Japanese ovarian cancer

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Abstract Ovarian cancer is an intractable disease and comprises a number of histological subtypes that are associated with clinical characteristics such as therapeutic efficacy and likelihood of relapse. Since ovarian cancer exhibits heterogeneity even within a same histological subtype, it is critical to develop a complementary classification framework, in which clinicopathological and biological features are associated with each subtype. Previously, for endometrial cancer, a molecular subtyping scheme based on genomic features was developed by The Cancer Genome Atlas (TCGA) and the scheme has been currently integrated into the system of 2020 WHO classification of Female Genital Tract tumor. A similar classification scheme has been needed developed for ovarian cancer diagnosis for further clinical stratification. Whereas genomic features can be utilized for this purpose because of the tight relationship with clinical manifestations, previous large-scale genomic studies of ovarian cancer have been conducted mainly with high-grade serous (HGS) histology, a major histological subtype in Caucasian. The remaining histologies exemplified by clear cell carcinoma, which is uniquely prevalent in the East Asian population, have not been covered by these studies, and therefore genomic features that can be utilized for molecular subtyping have not been well characterized for non-HGS ovarian cancer. To link genomic features with histological subtypes and to obtain wealthy information for further potential genomic stratification, we conducted genome sequencing analyses of 1,412 Japanese ovarian cancers across 6 major histotypes (clear cell, high-grade serous, endometrioid, mucinous, carcinosarcoma and sex cord-stromal). Using copy number information derived from sequenced data, we identified a novel copy number subtype, which is uniquely associated with clinicopathological and genomic attributes. The results will be presented focusing on the genomic features including germline mutations, somatic driver events and mutational signatures, in association with histological and molecular subtypes. Citation Format: Osamu Gotoh, Norio Tanaka, Tomoko Kaneyasu, Seiichi Mori, Tetsuo Noda. Genomic features of histological and molecular subtypes in Japanese ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6606.

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