Abstract GMM-052: EVIDENCE FOR APOBEC MUTAGENESIS IN CLEAR CELL OVARIAN CARCINOMA

Abstract

Abstract Clear cell ovarian carcinoma (CCOC) accounts for 1-12% of ovarian epithelial cancers and, notwithstanding early diagnosis, often has poor clinical outcomes. CCOC genomic sequences show strong cytosine to thymine (C-to-T) transition mutation biases (Wang et al., 2017, Nature Genetics; Maru et al., 2017, Gynecologic Oncology; Shibuya et al., 2018, Genes Chromosomes Cancer). Many of these mutations occur in APOBEC signature motifs (5'-TCA or TCT), implicating at least one of the nine APOBEC DNA cytosine deaminase family members in CCOC mutation and evolution. Three of the nine family members associate with cancer mutagenesis, but only one, APOBEC3B (A3B), correlates in multiple cancer types with worse clinical outcomes including overall and metastasis-free survival. Here, we further investigate the specific involvement of APOBEC mutagenesis in CCOC. First, we show that tumors positive for APOBEC signature mutations associate with poor clinical outcomes in comparison to those that do not. Second, we perform a comprehensive analysis of mutation signatures from new whole genome sequences and APOBEC expression profiles from tumor and normal tissues, including RTqPCR for mRNA quantification and immunohistochemistry to distinguish APOBEC protein expression in tumor cells from surrounding connective tissue and immune cells. Our results indicate a significant role for APOBEC mutagenesis in CCOC warranting further studies including evaluation of APOBEC as a prognostic biomarker. Citation Format: Artur S. Serebrenik, Matthew C. Jarvis, Prokopios P. Argyris, William B. Brown, Reuben S. Harris. EVIDENCE FOR APOBEC MUTAGENESIS IN CLEAR CELL OVARIAN CARCINOMA [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr GMM-052.