Liquid biopsy epigenomic profiling for cancer subtyping

Sylvan C. Baca(Broad Institute), Ji-Heui Seo(Dana-Farber Cancer Institute), Matthew P. Davidsohn(Dana-Farber Cancer Institute), Brad Fortunato(Broad Institute), Karl Semaan(Broad Institute), Shahabbedin Sotudian(Broad Institute), Gitanjali Lakshminarayanan(Dana-Farber Cancer Institute), Miklós Dióssy(Boston Children's Hospital), Xintao Qiu(Dana-Farber Cancer Institute), Talal El Zarif(Dana-Farber Cancer Institute), Hunter Savignano(Dana-Farber Cancer Institute), John Canniff(Dana-Farber Cancer Institute), Ikenna Madueke(Dana-Farber Cancer Institute), Renée Maria Saliby(Dana-Farber Cancer Institute), Ziwei Zhang(Broad Institute), Rong Li(Dana-Farber Cancer Institute), Yijia Jiang(Dana-Farber Cancer Institute), Len Taing(Dana-Farber Cancer Institute), Mark M. Awad(Harvard University), Cindy H. Chau(National Institutes of Health), James A. DeCaprio(Brigham and Women's Hospital), William D. Figg(National Institutes of Health), Tim F. Greten(National Institutes of Health), Aaron N. Hata(Harvard University), F. Stephen Hodi(Dana-Farber Cancer Institute), Melissa E. Hughes(Dana-Farber Cancer Institute), Keith L. Ligon(Dana-Farber Cancer Institute), Nancy U. Lin(Dana-Farber Cancer Institute), Kimmie Ng(Dana-Farber Cancer Institute), Matthew G. Oser(Dana-Farber Cancer Institute), Catherine B. Meador(Harvard University), Heather A. Parsons(Dana-Farber Cancer Institute), Mark M. Pomerantz(Dana-Farber Cancer Institute), Arun Rajan(National Cancer Institute), Jerome Ritz(Dana-Farber Cancer Institute), Manisha Thakuria(Brigham and Women's Hospital), Sara M. Tolaney(Dana-Farber Cancer Institute), Patrick Y. Wen(Brigham and Women's Hospital), Henry W. Long(Dana-Farber Cancer Institute), Jacob E. Berchuck(Dana-Farber Cancer Institute), Zoltán Szállási(Semmelweis University), Toni K. Choueiri(Dana-Farber Cancer Institute), Matthew L. Freedman(Broad Institute)
Nature Medicine
October 21, 2023
10.1038/s41591-023-02605-z
Cited by 113Open Access
Full Text

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.

Related Papers

BEDTools: a flexible suite of utilities for comparing genomic features
Aaron R. Quinlan, Ira M. Hall|Bioinformatics|2010|30.3k
Tissue-based map of the human proteome
Mathias Uhlén, Linn Fagerberg, Björn M. Hallström et al.|Science|2015|15.8k
ChIPseeker: an R/Bioconductor package for ChIP peak annotation, comparison and visualization
Guangchuang Yu, Li-Gen Wang, Qing‐Yu He|Bioinformatics|2015|4.7k
Histone H3K27ac separates active from poised enhancers and predicts developmental state
Menno P. Creyghton, Albert W. Cheng, G. Grant Welstead et al.|Proceedings of the National Academy of Sciences|2010|4.5k
Cell-free DNA Comprises an In Vivo Nucleosome Footprint that Informs Its Tissues-Of-Origin
Matthew W. Snyder, Martin Kircher, Andrew J. Hill et al.|Cell|2016|1.5k