Liquid biopsy epigenomic profiling for cancer subtyping

Sylvan C. Baca, Ji Heui Seo, Matthew P. Davidsohn, Brad Fortunato, Karl Semaan, Shahabbedin Sotudian, Gitanjali Lakshminarayanan, Miklos Diossy, Xintao Qiu, Talal El Zarif, Hunter Savignano, John Canniff, Ikenna Madueke, Renee Maria Saliby, Ziwei Zhang, Rong Li, Yijia Jiang, Len Taing, Mark Awad, Cindy H. ChauJames A. DeCaprio, William D. Figg, Tim F. Greten, Aaron N. Hata, F. Stephen Hodi, Melissa E. Hughes, Keith L. Ligon, Nancy Lin, Kimmie Ng, Matthew G. Oser, Catherine Meador, Heather A. Parsons, Mark M. Pomerantz, Arun Rajan, Jerome Ritz, Manisha Thakuria, Sara M. Tolaney, Patrick Y. Wen, Henry Long, Jacob E. Berchuck, Zoltan Szallasi, Toni K. Choueiri, Matthew L. Freedman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish
Pages (from-to)2737-2741
Number of pages5
JournalNature Medicine
Volume29
Issue number11
DOIs
StatePublished - Nov 2023
Externally publishedYes

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