LINE-1 ORF1p expression occurs in clear cell ovarian carcinoma precursors and is a candidate blood biomarker
Long interspersed element 1 (LINE-1) retrotransposons are repetitive sequences that can move within the genome by an autonomous mechanism. To limit their mutagenic potential, benign cells restrict LINE-1 expression through molecular mechanisms such as DNA methylation and histone modification, but these mechanisms are usually impaired in cancer. Clear cell ovarian carcinoma (CCOC) represents 5-10% of ovarian cancers and is thought to arise from endometriosis. Women with advanced CCOC face poor prognoses, highlighting the importance of understanding early disease pathogenesis. In our study, 33 of 40 cases (over 82%) of CCOC tumors express ORF1p, a LINE-1-encoded protein. We found that LINE-1 de-repression is an early event in CCOC, as ORF1p is enhanced during the transition from typical to atypical endometriosis and persists in invasive cancer. Finally, using single-molecule array (Simoa) assays, we detected ORF1p in patient blood, suggesting it as a potential minimally invasive biomarker for this disease.
Authors
- Gabriel Mingo (ORCID: https://orcid.org/0000-0002-7593-5885)
- Yelena Zhuravlev
- Carlos Parra‐Herran (ORCID: https://orcid.org/0000-0003-1420-7291)
- Sagar Rayamajhi (ORCID: https://orcid.org/0000-0001-5420-7873)
- Yi Feng (ORCID: https://orcid.org/0000-0003-1493-1968)
- Dalia K. Omran (ORCID: https://orcid.org/0000-0003-4323-2621)
- Ernst Lengyel (ORCID: https://orcid.org/0000-0001-8624-1507)
- Stephanie J. Zhang (ORCID: https://orcid.org/0000-0001-6308-5257)
- Martin S. Taylor (ORCID: https://orcid.org/0000-0001-5824-142X)
- Andrew K. Godwin (ORCID: https://orcid.org/0000-0002-3987-9580)
- János L. Tanyi (ORCID: https://orcid.org/0000-0002-5657-3698)
- Pamela Santiago (ORCID: https://orcid.org/0000-0002-0360-1026)
- Connie Wu
- Agnes Julia Bilecz (ORCID: https://orcid.org/0000-0002-5231-2669)
- Ronny Drapkin (ORCID: https://orcid.org/0000-0002-6912-6977)
- Kathleen H. Burns (ORCID: https://orcid.org/0000-0003-1620-3761)
- Euihye Jung (ORCID: https://orcid.org/0000-0003-1202-247X)
- Kyle M. Devins (ORCID: https://orcid.org/0000-0002-8097-2437)
- Mark A. Morgan (ORCID: https://orcid.org/0000-0001-5245-1709)
- Meaghan C. Dougher
- David R. Walt (ORCID: https://orcid.org/0000-0002-5524-7348)
- Hannah S. Rendulich
- Sho Sato (ORCID: https://orcid.org/0000-0001-5628-7141)
- Sarah Kim (ORCID: https://orcid.org/0000-0003-2290-6025)
- Lauren E. Schwartz
- Ie‐Ming Shih
- Tian-Li Wang
Institutions
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Johns Hopkins University (US)
- Hospital of the University of Pennsylvania (US)
- Johns Hopkins Medicine (US)
- University of Chicago (US)
- Massachusetts General Hospital (US)
- Dana-Farber Cancer Institute (US)
- Cancer Research Center (US)
- Penn Center for AIDS Research (US)
- University of Kansas Medical Center (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- npj Precision Oncology
- Published
- 2025-03-06
- DOI
- https://doi.org/10.1038/s41698-025-00849-1
- Citations
- 6
- Primary Topic
- Viral-associated cancers and disorders
- Type
- article
- Field-Weighted Citation Impact
- 6.27