Liquid biopsy epigenomic profiling for cancer subtyping
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Published:2023-10-21
Issue:11
Volume:29
Page:2737-2741
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ISSN:1078-8956
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Container-title:Nature Medicine
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language:en
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Short-container-title:Nat Med
Author:
Baca Sylvan C., Seo Ji-Heui, Davidsohn Matthew P., Fortunato Brad, Semaan Karl, Sotudian ShahabbedinORCID, Lakshminarayanan Gitanjali, Diossy Miklos, Qiu XintaoORCID, El Zarif Talal, Savignano Hunter, Canniff John, Madueke Ikenna, Saliby Renee MariaORCID, Zhang Ziwei, Li RongORCID, Jiang Yijia, Taing Len, Awad Mark, Chau Cindy H.ORCID, DeCaprio James A.ORCID, Figg William D.ORCID, Greten Tim F.ORCID, Hata Aaron N.ORCID, Hodi F. Stephen, Hughes Melissa E., Ligon Keith L.ORCID, Lin Nancy, Ng KimmieORCID, Oser Matthew G.ORCID, Meador Catherine, Parsons Heather A.ORCID, Pomerantz Mark M., Rajan ArunORCID, Ritz JeromeORCID, Thakuria Manisha, Tolaney Sara M.ORCID, Wen Patrick Y., Long HenryORCID, Berchuck Jacob E.ORCID, Szallasi ZoltanORCID, Choueiri Toni K.ORCID, Freedman Matthew L.ORCID
Abstract
AbstractAlthough circulating tumor DNA (ctDNA) assays are increasingly used to inform clinical decisions in cancer care, they have limited ability to identify the transcriptional programs that govern cancer phenotypes and their dynamic changes during the course of disease. To address these limitations, we developed a method for comprehensive epigenomic profiling of cancer from 1 ml of patient plasma. Using an immunoprecipitation-based approach targeting histone modifications and DNA methylation, we measured 1,268 epigenomic profiles in plasma from 433 individuals with one of 15 cancers. Our assay provided a robust proxy for transcriptional activity, allowing us to infer the expression levels of diagnostic markers and drug targets, measure the activity of therapeutically targetable transcription factors and detect epigenetic mechanisms of resistance. This proof-of-concept study in advanced cancers shows how plasma epigenomic profiling has the potential to unlock clinically actionable information that is currently accessible only via direct tissue sampling.
Funder
U.S. Department of Defense U.S. Department of Health & Human Services | NIH | National Cancer Institute
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology,General Medicine
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28 articles.
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