Genomic landscape of endometrial, ovarian and cervical cancers in Japan from database in the Center for Cancer Genomics and Advanced Therapeutics.

Abstract

ObjectiveThis study aimed to comprehensively clarify genomic landscape, and its association with tumor mutation burden-high (TMB-H, [greater double equals]10 mut/Mb) and microsatellite instability-high (MSI-H) in endometrial, cervical, and ovarian cancers. MethodsWe obtained genomic datasets of a comprehensive genomic profiling test, FoundationOne(R) CDx, with clinical information by using the "Center for Cancer Genomics and Advanced Therapeutics" (C-CAT) database in Japan. The patients could take the tests only after the standardized treatments under universal health insurance coverage. ResultsEndometrial cancers (n=561) were characterized by high frequency of tumor mutational burden-high (TMB-H) (13.9%) and MSI-high (MSI-H) (10.8%), especially in endometrioid carcinomas. The lower ratio of POLE exonuclease mutations (1.4%) and higher ratio of TP53 mutations (54.4%) than previous reports suggested the prognostic impact of the molecular subtypes. Among 839 cervical cancers, frequent mutations of KRAS (32.2%), TP53 (29.4%), PIK3CA (22.2%), STK11 (22.2%), CDKN2A (18.3%), and ERBB2 (16.7%) were observed in adenocarcinomas, while the ratio of TMB-H was significantly higher in squamous cells carcinomas (20.6%). Among 1,606 ovarian cancers, genomic profiling of serous (n=784), clear cell (n=333), endometrioid (n=92), and mucinous carcinomas (n=91) was characterized. Pathogenic mutations in the POLE exonuclease domain were linked to high TMB (TMB >100 mut/Mb), and the mutation ratio was low in both cervical (0.0%) and ovarian cancer (0.19%). ConclusionThe C-CAT database is useful to provide mutational landscape of each cancer type and each histological subtype. As the dataset is collected exclusively from patients after the standardized treatments, the information of "druggable" alterations highlights the unmet needs for drug development in major gynecological cancers.