@article{71f6950a357c4f9f96458ca206320c44,
title = "Liquid biopsy epigenomic profiling for cancer subtyping",
abstract = "Although 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.",
author = "Baca, {Sylvan C.} and Seo, {Ji Heui} and Davidsohn, {Matthew P.} and Brad Fortunato and Karl Semaan and Shahabbedin Sotudian and Gitanjali Lakshminarayanan and Miklos Diossy and Xintao Qiu and {El Zarif}, Talal and Hunter Savignano and John Canniff and Ikenna Madueke and Saliby, {Renee Maria} and Ziwei Zhang and Rong Li and Yijia Jiang and Len Taing and Mark Awad and Chau, {Cindy H.} and DeCaprio, {James A.} and Figg, {William D.} and Greten, {Tim F.} and Hata, {Aaron N.} and Hodi, {F. Stephen} and Hughes, {Melissa E.} and Ligon, {Keith L.} and Nancy Lin and Kimmie Ng and Oser, {Matthew G.} and Catherine Meador and Parsons, {Heather A.} and Pomerantz, {Mark M.} and Arun Rajan and Jerome Ritz and Manisha Thakuria and Tolaney, {Sara M.} and Wen, {Patrick Y.} and Henry Long and Berchuck, {Jacob E.} and Zoltan Szallasi and Choueiri, {Toni K.} and Freedman, {Matthew L.}",
note = "Funding Information: The authors thank M. Merino for providing the HER2 IHC staining. This work is supported by the US Department of Defense (DoD) (awards W81XWH-21-1-0358 and W81XWH-21-1-0299 to S.C.B. and W81XWH-18-2-0056 to Z.S.); the National Cancer Institute (R01 CA137008 to A.N.H.); the Breast Cancer Research Foundation (BCRF-21-159 to Z.S.); Kr{\ae}ftens Bek{\ae}mpelse (R281-A16566 and R342-A19788 to Z.S.); Det Frie Forskningsr{\aa}d Sundhed og Sygdom (7016-00345B to Z.S.); National Institutes of Health P01 CA228696-01A1 to Z.S. and M.L.F.; and the University of Massachusetts Boston–Dana-Farber/Harvard Cancer Center U54 Partnership Grant (UMass Boston: 2 U54 CA156734-12; DF/HCC: 2 U54 CA156732-12). M.L.F. is supported by the Claudia Adams Barr Program for Innovative Cancer Research, the Dana-Farber Cancer Institute Presidential Initiatives Fund, the H.L. Snyder Medical Research Foundation, the Cutler Family Fund for Prevention and Early Detection, the Donahue Family Fund, W81XWH-21-1-0339 and W81XWH-22-1-0951 (DoD) and the Movember PCF Challenge Award. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Funding Information: S.C.B., T.K.C. and M.L.F. are co-founders and shareholders of Precede Biosciences. J.D. is a consultant for Kymera Therapeutics and has a sponsored research agreement with Kymera Therapeutics. M.T. served on an advisory board for Incyte. A.N.H. reports research support from Amgen, Blueprint Medicines, BridgeBio, Bristol-Myers Squibb, C4 Therapeutics, Eli Lilly, Novartis, Nuvalent, Pfizer, Roche/Genentech and Scorpion Therapeutics and paid consulting for Engine Biosciences, Nuvalent, Oncovalent, TigaTx and Tolremo Therapeutics. J.R. receives research funding from Equillium, Kite/Gilead, Novartis and Oncternal and consults or is on advisory boards for AvroBio, Akron Biotech, Clade Therapeutics, Garuda Therapeutics, LifeVault Bio, Novartis, Smart Immune and TScan Therapeutics. The remaining authors report no competing interests. Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2023",
doi = "10.1038/s41591-023-02605-z",
language = "English",
journal = "Nature Medicine",
issn = "1078-8956",
}