Abstract 1055: ORF1p expression from LINE-1 occurs in clear cell ovarian carcinoma precursors and is detectable in patients’ plasma samples

Abstract

Abstract Long interspersed element 1 (LINE-1) retrotransposons are repetitive genomic sequences able to move across the genome by an autonomous “copy and paste” mechanism. Given the mutagenic potential of LINE-1, benign cells restrict its expression, although the molecular mechanisms involved are usually impaired in cancer. Clear cell ovarian carcinoma (CCOC) accounts for ~5-10% of ovarian cancers and is believed to arise from endometriosis. Women have a poor prognosis when it presents at an advanced stage, which emphasizes the need for a better understanding of the disease. In the present study, we found that ~85% of CCOC tumors express ORF1p, one of two proteins encoded by LINE-1. We show that CCOC cell lines retain ORF1p expression and release it into the extracellular media. By using single molecule array (Simoa) assays, we detected ORF1p in patient plasma, proposing ORF1p as a non-invasive biomarker for this disease. Finally, we found that LINE-1 retrotransposon de-repression is an early event in CCOC, as ORF1p is enhanced during the transition from typical to atypical endometriosis and that is retained in the invasive cancer. Citation Format: Pamela R. de Santiago, Sho Sato, Yelena Zhuravlev, Hannah S. Rendulich, Marty S. Taylor, Connie Wu, Meaghan C. Dougher, Lauren Schwartz, David R. Walt, Kathleen H. Burns, Ronny Drapkin. ORF1p expression from LINE-1 occurs in clear cell ovarian carcinoma precursors and is detectable in patients’ plasma samples [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(6_Suppl):Abstract nr 1055.