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

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

doi:10.1038/s41698-025-00849-1

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

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^*

^*Corresponding author for this work

School of Medicine

University of Pennsylvania
Brigham and Women’s Hospital
Harvard University
The University of Chicago
University of Kansas
Massachusetts General Hospital
Johns Hopkins University
Dana-Farber Cancer Institute

Research output: Contribution to journal › Journal Article › peer-review

5 Scopus citations

Abstract

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.

Original language	English
Article number	62
Pages (from-to)	62
Journal	npj Precision Oncology
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41698-025-00849-1
State	Published - 06 03 2025

Bibliographical note

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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10.1038/s41698-025-00849-1

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de Santiago, P. R., Sato, S., Zhang, S. J., Dougher, M. C., Devins, K. M., Bilecz, A. J., Rayamajhi, S., Mingo, G., Rendulich, H. S., Feng, Y., Wu, C., Taylor, M. S., Zhuravlev, Y., Jung, E., Omran, D. K., Wang, T. L., Shih, I. M., Schwartz, L. E., Kim, S., ... Drapkin, R. (2025). LINE-1 ORF1p expression occurs in clear cell ovarian carcinoma precursors and is a candidate blood biomarker. npj Precision Oncology, 9(1), 62. Article 62. https://doi.org/10.1038/s41698-025-00849-1

@article{e36d4b8ec9a34ebca82cc9cb3194102f,

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

abstract = "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.",

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

note = "{\textcopyright} 2025. The Author(s).",

year = "2025",

month = mar,

day = "6",

doi = "10.1038/s41698-025-00849-1",

language = "英语",

volume = "9",

pages = "62",

journal = "npj Precision Oncology",

issn = "2397-768X",

publisher = "Nature Research",

number = "1",

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de Santiago, PR, Sato, S, Zhang, SJ, Dougher, MC, Devins, KM, Bilecz, AJ, Rayamajhi, S, Mingo, G, Rendulich, HS, Feng, Y, Wu, C, Taylor, MS, Zhuravlev, Y, Jung, E, Omran, DK, Wang, TL, Shih, IM, Schwartz, LE, Kim, S, Morgan, MA, Tanyi, JL, Burns, KH, Lengyel, E, Parra-Herran, C, Godwin, AK, Walt, DR & Drapkin, R 2025, 'LINE-1 ORF1p expression occurs in clear cell ovarian carcinoma precursors and is a candidate blood biomarker', npj Precision Oncology, vol. 9, no. 1, 62, pp. 62. https://doi.org/10.1038/s41698-025-00849-1

TY - JOUR

T1 - LINE-1 ORF1p expression occurs in clear cell ovarian carcinoma precursors and is a candidate blood biomarker

AU - de Santiago, Pamela R.

AU - Sato, Sho

AU - Zhang, Stephanie J.

AU - Dougher, Meaghan C.

AU - Devins, Kyle M.

AU - Bilecz, Agnes J.

AU - Rayamajhi, Sagar

AU - Mingo, Gabriel

AU - Rendulich, Hannah S.

AU - Feng, Yi

AU - Wu, Connie

AU - Taylor, Martin S.

AU - Zhuravlev, Yelena

AU - Jung, Euihye

AU - Omran, Dalia K.

AU - Wang, Tian Li

AU - Shih, Ie Ming

AU - Schwartz, Lauren E.

AU - Kim, Sarah

AU - Morgan, Mark A.

AU - Tanyi, Janos L.

AU - Burns, Kathleen H.

AU - Lengyel, Ernst

AU - Parra-Herran, Carlos

AU - Godwin, Andrew K.

AU - Walt, David R.

AU - Drapkin, Ronny

PY - 2025/3/6

Y1 - 2025/3/6

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/86000285849

U2 - 10.1038/s41698-025-00849-1

DO - 10.1038/s41698-025-00849-1

M3 - 文章

C2 - 40050409

AN - SCOPUS:86000285849

SN - 2397-768X

VL - 9

SP - 62

JO - npj Precision Oncology

JF - npj Precision Oncology

IS - 1

M1 - 62

ER -

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

Abstract

Bibliographical note

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