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<p>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.</p>

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LINE-1 ORF1p expression occurs in clear cell ovarian carcinoma precursors and is a candidate blood biomarker

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月6日

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  • Pamela R. de Santiago,
  • Sho Sato,
  • Stephanie J. Zhang,
  • Meaghan C. Dougher,
  • Kyle M. Devins,
  • Agnes J. Bilecz,
  • Sagar Rayamajhi,
  • Gabriel Mingo,
  • Hannah S. Rendulich,
  • Yi Feng,
  • Connie Wu,
  • Martin S. Taylor,
  • Yelena Zhuravlev,
  • Euihye Jung,
  • Dalia K. Omran,
  • Tian-Li Wang,
  • Ie-Ming Shih,
  • Lauren E. Schwartz,
  • Sarah Kim,
  • Mark A. Morgan,
  • Janos L. Tanyi,
  • Kathleen H. Burns,
  • Ernst Lengyel,
  • Carlos Parra-Herran,
  • Andrew K. Godwin,
  • David R. Walt,
  • Ronny Drapkin

摘要

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.