Abstract 1529: Ovarian low grade serous cancer: Mutation analysis with a comprehensive 409 cancer gene panel

Abstract

Abstract Patients with ovarian serous cancer are usually younger and survive longer than patients with high-grade serous cancer. Unfortunately, most low-grade serous cancer patients eventually die of the disease because recurrent low-grade serous carcinoma is relative chemoresistant. So far, the known mutations identified in low-grade ovarian serous carcinomas and their putative precursor ovarian serous borderline tumors are BRAF and KRAS mutations. BRAF and KRAS mutations together have been identified in approximately 60% of serous borderline tumors and early stage low-grade serous carcinomas. However, BRAF mutation is rare in advanced-stage low-grade serous carcinomas. To further investigate the molecular pathogenesis of low-grade serous carcinoma, mutation analyses of 409 cancer related genes were performed in 21 low-grade ovarian serous carcinoma, 8 ovarian serous borderline tumors and one ovarian cystadenoma using next generation sequencer. A total of nineteen missense mutations were identified in 20 samples but ten samples had no detectable mutations. BRAF mutation was detected in 3 serous borderline tumors and one low-grade serous carcinoma. KRAS mutations were detected in three low-grade serous carcinomas. Other than BRAF and KRAS mutations, we also detected other prevalent mutations: ATRX mutations were detected in 3 low-grade ovarian serous carcinomas and a cystadenoma; KMT2C mutations were detected in 3 low-grade ovarian serous carcinomas; ATM mutations were detected in 2 low-grade ovarian serous carcinomas. Interestingly, both ATRX and MLL3 genes are involved in the chromatin remodeling. Moreover, both ATRX and ATM are involved in DNA damaging response. Thus, the pathogenesis of low-grade serous carcinoma may involve de-regulation of chromatin remodeling pathway and DNA damaging response. Further analysis of a large cohort of low-grade serous carcinomas for these prevalent mutations is ongoing. Citation Format: Yvonne TM Tsang, Daisy Izaguirre, Suet-Yan Kwan, Samuel C. Mok, David Gershenson, Kwong-Kwok Wong. Ovarian low grade serous cancer: Mutation analysis with a comprehensive 409 cancer gene panel. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1529. doi:10.1158/1538-7445.AM2014-1529