Liquid biopsy epigenomic profiling for cancer subtyping

作者：Sylvan C. Baca, Ji-Heui Seo, Matthew P. Davidsohn, Brad Fortunato, Karl Semaan, Shahabbedin Sotudian, Gitanjali Lakshminarayanan, Miklós Dióssy, Xintao Qiu, Talal El Zarif, Hunter Savignano, John Canniff, Ikenna Madueke, Renée Maria Saliby, Ziwei Zhang, Rong Li, Yijia Jiang, Len Taing, Mark M. Awad, Cindy H. Chau, James A. DeCaprio, William D. Figg, Tim F. Greten, Aaron N. Hata, F. Stephen Hodi, Melissa E. Hughes, Keith L. Ligon, Nancy U. Lin, Kimmie Ng, Matthew G. Oser, Catherine B. Meador, Heather A. Parsons, Mark M. Pomerantz, Arun Rajan, Jerome Ritz, Manisha Thakuria, Sara M. Tolaney, Patrick Y. Wen, Henry W. Long, Jacob E. Berchuck, Zoltán Szállási, Toni K. Choueiri, Matthew L. Freedman · 发表于：Nature Medicine · 年份：2023 · DOI：10.1038/s41591-023-02605-z · 被引用次数：126 · 研究领域：Epigenetics and DNA Methylation、Cancer Genomics and Diagnostics、RNA modifications and cancer

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.