ArticleCancer discovery2023
Ultrasensitive Detection of Circulating LINE-1 ORF1p as a Specific Multicancer Biomarker.
Erratum issuedOpen access · hybridAbstract read
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Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 61 papers.
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61citing papers in PubMed
11.7field-weighted citation impact, top 1% of its field
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Who cites it
61 citing papers in PubMed, 76 citations in OpenAlex.
- Viral mimicry escape as a necessary feature of malignant transformation.Nature reviews. Cancer · 2026Review
- LINE-1 Deregulation in Ovarian Cancer: Implications for Diagnosis, Prognosis, and Therapeutic Targeting.Molecular diagnosis & therapy · 2026Review
- Transposable Element Activation: A Hallmark of Cancer.Cancer discovery · 2026Review
- Variation in LINE-1 ORF1p expression across histologic and demographic subgroups in non-small cell lung cancers.Translational oncology · 2026Article
- LINE-1 insertion intermediates recombine with one another or with DNA breaks to form genome rearrangements.Nature communications · 2026Article
- Epigenomic modifications define chromatin states to regulate cell-free DNA fragmentomics.Nature communications · 2026Article
- Advancements and Clinical Applications Prospects of Epigenetic Biomarkers in Liquid Biopsy for Oral Squamous Cell Carcinoma.Current issues in molecular biology · 2026Review
- Detection of endogenous LINE-1 ORF2p and its potent reverse transcriptase activity in the MCF-7 breast cancer cell line.The FEBS journal · 2026Article
- LINE-1 retrotransposons: Multifaceted functions and regulatory mechanisms in health and disease.Molecular therapy. Nucleic acids · 2026Review
- Rethinking ovarian cancer III: the past decade and future directions.Nature reviews. Cancer · 2026Review
- Locus-specific LINE-1 mRNA expression reflects cell-type- and stimulus-specific senescence states.Nucleic acids research · 2026Article
- Functional analyses identify the L1 ORF2p Cryptic domain as a hub for intramolecular interfaces required for retrotransposition.Nucleic acids research · 2026Article
- LINE-1 Locus Transcription Nucleates Oncogenic Chromatin Architecture.Cancer discovery · 2026Article
- Transposable elements in the dark genome.Nature biotechnology · 2026Article
- Ultrasensitive Enzyme-Free Detection of Proteins on Magnetic Beads.Journal of the American Chemical Society · 2026Article
- LINE-1 retrotransposition modulates metabolic stress and promotes cuproptosis resistance in lung squamous cell carcinoma by disrupting mitochondrial membrane homeostasis.Journal of translational medicine · 2026Article
- LINE-1 retrotransposition is a recurrent cause ofbioRxiv : the preprint server for biology · 2026Article
- Retroelements in thyroid cancer: epigenetic plasticity, dedifferentiation, and therapeutic opportunities.Reviews in endocrine & metabolic disorders · 2026Review
- Article
- Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
- Update of
Authors and funding
59 authors at 12 institutions in 2 countries.
Martin S Taylor *Department of Pathology, Mass General Brigham and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-5824-142X
Connie Wu *Department of Pathology, Mass General Brigham and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-4031-7286
Peter C FridyLaboratory of Cellular and Structural Biology, The Rockefeller University, New York, New York.ORCID 0000-0002-8208-9154
Stephanie J ZhangDepartment of Pathology, Mass General Brigham and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-6308-5257
Yasmeen SenussiDepartment of Pathology, Mass General Brigham and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-6881-5455
Justina C WoltersDepartment of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID 0000-0003-0066-3720
Tatiana CajusoDepartment of Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-6354-5572
Wen-Chih ChengDepartment of Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0009-0005-5034-6995
John D HeapsDepartment of Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0009-0005-5871-5345
Bryant D MillerDepartment of Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0009-0006-9145-8499
Kei MoriDepartment of Pathology, Mass General Brigham and Harvard Medical School, Boston, Massachusetts.ORCID 0009-0009-7421-5307
Limor CohenDepartment of Pathology, Mass General Brigham and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0003-1448-0925
Hua JiangLaboratory of Cellular and Structural Biology, The Rockefeller University, New York, New York.ORCID 0009-0008-2059-3057
Kelly R MolloyLaboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, New York.ORCID 0009-0006-3142-4481
Brian T ChaitLaboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, New York.ORCID 0000-0003-3524-557X
Michael G GogginsJohns Hopkins University School of Medicine, Baltimore, Maryland.ORCID 0000-0002-4286-2296
Irun BhanMass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-2163-0488
Joseph W FransesMass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-2517-4950
Xiaoyu YangDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0009-0001-0035-9289
Mary-Ellen TaplinDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-3384-0300
Xinan WangDepartment of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.ORCID 0000-0001-5236-1105
David C ChristianiMass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-0301-0242
Bruce E JohnsonDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-5252-3677
Matthew MeyersonDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-9133-8108
Ravindra UppaluriDepartment of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-5988-6828
Ann Marie EgloffDepartment of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-1182-2793
Elyssa N DenaultMass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0009-0003-7788-0827
Laura M SpringMass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-8904-3514
Tian-Li WangJohns Hopkins University School of Medicine, Baltimore, Maryland.ORCID 0000-0002-7082-449X
Ie-Ming ShihJohns Hopkins University School of Medicine, Baltimore, Maryland.ORCID 0000-0002-1084-2071
Jennifer E FairmanJohns Hopkins University School of Medicine, Baltimore, Maryland.ORCID 0000-0002-2319-1773
Euihye JungUniversity of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.ORCID 0000-0003-1202-247X
Kshitij S AroraDepartment of Pathology, Mass General Brigham and Harvard Medical School, Boston, Massachusetts.ORCID 0009-0004-9254-612X
Osman H YilmazDepartment of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-9822-7112
Sonia CohenDepartment of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0003-0172-5620
Tatyana SharovaDepartment of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0003-2123-3906
Gary ChiMass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0009-0003-5374-4214
Bryanna L NordenMass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0003-2084-473X
Yuhui SongMass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-5087-4684
Linda T NiemanMass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-0141-8308
Leontios PappasMass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-0589-8265
Aparna R ParikhMass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-5245-7841
Matthew R StricklandMass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-7845-0712
Ryan B CorcoranMass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-8173-5778
Tomas MustelinDivision of Rheumatology, Department of Medicine, University of Washington, Seattle, Washington.ORCID 0000-0001-5912-8840
George EngDepartment of Pathology, Mass General Brigham and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0003-0272-9623
Ömer H YilmazDepartment of Pathology, Mass General Brigham and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-7577-4612
Ursula A MatulonisDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-3103-6992
Andrew T ChanClinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-7284-6767
Steven J SkatesMGH Biostatistics, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-9249-4316
Bo R RuedaDepartment of Obstetrics and Gynecology, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0001-9489-8699
Ronny DrapkinUniversity of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.ORCID 0000-0002-6912-6977
Samuel J KlempnerMass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-4062-0808
Vikram DeshpandeDepartment of Pathology, Mass General Brigham and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0003-4230-9308
David T TingMass General Cancer Center and Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-3261-2322
Michael P RoutLaboratory of Cellular and Structural Biology, The Rockefeller University, New York, New York.ORCID 0000-0003-2010-706X
John LaCavaLaboratory of Cellular and Structural Biology, The Rockefeller University, New York, New York.ORCID 0000-0002-6307-7713
David R Walt *Department of Pathology, Mass General Brigham and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0002-5524-7348
Kathleen H BurnsDepartment of Pathology, Mass General Brigham and Harvard Medical School, Boston, Massachusetts.ORCID 0000-0003-1620-3761
Massachusetts General Hospital · USDana-Farber Cancer Institute · USRockefeller University · USJohns Hopkins University · USHarvard University · USBeth Israel Deaconess Medical Center · USBrigham and Women's Hospital · USUniversity Medical Center Groningen · NLUniversity of Pennsylvania · USHarvard University Press · USLouisiana State University in Shreveport · USUniversity of Washington · US
Funding
VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI JENNIFER W MACK · 1985 to 2026
$330.6MTissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI BASS, ADAM JOEL · 2007 to 2023
$33.2MSPORE in Ovarian CancerP50CA228991 · NCI · JOHNS HOPKINS UNIVERSITY · PI Ronny I DRAPKIN, IE-MING SHIH · 2018 to 2026
$20.5MTR&D Project 4. The Imaging Stage: Multiscale Spatiotemporal Modeling of Macromolecular Systems in Cellular NeighborhoodsP41GM109824 · NIGMS · ROCKEFELLER UNIVERSITY · PI ROUT, MICHAEL P · 2014 to 2023
$18.8MProject 2: Combined personal neoantigen-targeting cancer vaccines with immune checkpoint blockade for ovarian cancerP50CA240243 · NCI · DANA-FARBER CANCER INST · PI CASTRO, CESAR M · 2020 to 2024
$11.5MMOLECULAR IMMUNOLOGY AND TUMOR BIOLOGYT32CA009216 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI David Michael Langenau · 1985 to 2026
$10.6MProteomic, Genomic, and Longitudinal Pathways to Ovarian Cancer Biomarker DiscoveryU01CA152990 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BIRRER, MICHAEL, SKATES, STEVEN J · 2010 to 2021
$8.9MGenome-wide methylation and proteomic analysis of uterine lavage and cervical swab for early detection of ovarian cancerU2CCA271871 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Steven J Skates · 2022 to 2026
$4.5MLung Cancer Screening via Ultrasensitive and Cost-efficient Analysis of Tumor DNA Signatures in BloodU01CA233364 · NCI · YALE UNIVERSITY · PI PATEL, ABHIJIT, SKATES, STEVEN J · 2018 to 2022
$3.4MUnderstanding the Relationship of Repeat Expression and MetastasisR01CA240924 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI GREENBAUM, BENJAMIN, TING, DAVID TSAI · 2019 to 2023
$3.3MA Statistical Physics Framework for Understanding the Role of Repeat RNA in Tumor ImmunityU01CA228963 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI GREENBAUM, BENJAMIN, TING, DAVID TSAI · 2020 to 2024
$3.2MConsequences of retrotransposition on genome integrityR01CA276112 · NCI · DANA-FARBER CANCER INST · PI KATHLEEN H BURNS, Alice Eunjung Lee · 2023 to 2026
$2.9MNCI NIH HHS P30 CA006516NCI NIH HHS P50 CA127003NCI NIH HHS P50 CA228991NCI NIH HHS P50 CA240243NCI NIH HHS R01 CA240816NCI NIH HHS R01 CA240924NCI NIH HHS R01 CA276112NCI NIH HHS T32 CA009216NCI NIH HHS U01 CA152990NCI NIH HHS U01 CA228963NCI NIH HHS U01 CA233364NCI NIH HHS U2C CA271871NIBIB NIH HHS F32 EB029777NIDDK NIH HHS K08 DK129824NIGMS NIH HHS P41 GM109824NIGMS NIH HHS R01 GM126170NIGMS NIH HHS R01 GM130680
Abstract
Improved biomarkers are needed for early cancer detection, risk stratification, treatment selection, and monitoring treatment response. Although proteins can be useful blood-based biomarkers, many have limited sensitivity or specificity for these applications. Long INterspersed Element-1 (LINE-1) open reading frame 1 protein (ORF1p) is a transposable element protein overexpressed in carcinomas and high-risk precursors during carcinogenesis with negligible expression in normal tissues, suggesting ORF1p could be a highly specific cancer biomarker. To explore ORF1p as a blood-based biomarker, we engineered ultrasensitive digital immunoassays that detect mid-attomolar (10-17 mol/L) ORF1p concentrations in plasma across multiple cancers with high specificity. Plasma ORF1p shows promise for early detection of ovarian cancer, improves diagnostic performance in a multianalyte panel, provides early therapeutic response monitoring in gastroesophageal cancers, and is prognostic for overall survival in gastroesophageal and colorectal cancers. Together, these observations nominate ORF1p as a multicancer biomarker with potential utility for disease detection and monitoring. SIGNIFICANCE: The LINE-1 ORF1p transposon protein is pervasively expressed in many cancers and is a highly specific biomarker of multiple common, lethal carcinomas and their high-risk precursors in tissue and blood. Ultrasensitive ORF1p assays from as little as 25 μL plasma are novel, rapid, cost-effective tools in cancer detection and monitoring. See related commentary by Doucet and Cristofari, p. 2502. This article is featured in Selected Articles from This Issue, p. 2489.
Indexed as
CarcinomaOvarian NeoplasmsBiomarkers, TumorFemaleHumansLong Interspersed Nucleotide ElementsProteinsBiomarkers, TumorProteins
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