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author Baca, Sylvan C.
Seo, Ji-Heui
Davidsohn, Matthew P.
Fortunato, Brad
Semaan, Karl
Sotudian, Shahabbedin
Lakshminarayanan, Gitanjali
Diossy, Miklos
Qiu, Xintao
El Zarif, Talal
Savignano, Hunter
Canniff, John
Madueke, Ikenna
Saliby, Renee Maria
Zhang, Ziwei
Li, Rong
Jiang, Yijia
Taing, Len
Awad, Mark
Chau, Cindy H.
DeCaprio, James A.
Figg, William D.
Greten, Tim F.
Hata, Aaron N.
Hodi, F. Stephen
Hughes, Melissa E.
Ligon, Keith L.
Lin, Nancy
Ng, Kimmie
Oser, Matthew G.
Meador, Catherine
Parsons, Heather A.
Pomerantz, Mark M.
Rajan, Arun
Ritz, Jerome
Thakuria, Manisha
Tolaney, Sara M.
Wen, Patrick Y.
Long, Henry
Berchuck, Jacob E.
Szallasi, Zoltan
Choueiri, Toni K.
Freedman, Matthew L.
author_facet Baca, Sylvan C.
Seo, Ji-Heui
Davidsohn, Matthew P.
Fortunato, Brad
Semaan, Karl
Sotudian, Shahabbedin
Lakshminarayanan, Gitanjali
Diossy, Miklos
Qiu, Xintao
El Zarif, Talal
Savignano, Hunter
Canniff, John
Madueke, Ikenna
Saliby, Renee Maria
Zhang, Ziwei
Li, Rong
Jiang, Yijia
Taing, Len
Awad, Mark
Chau, Cindy H.
DeCaprio, James A.
Figg, William D.
Greten, Tim F.
Hata, Aaron N.
Hodi, F. Stephen
Hughes, Melissa E.
Ligon, Keith L.
Lin, Nancy
Ng, Kimmie
Oser, Matthew G.
Meador, Catherine
Parsons, Heather A.
Pomerantz, Mark M.
Rajan, Arun
Ritz, Jerome
Thakuria, Manisha
Tolaney, Sara M.
Wen, Patrick Y.
Long, Henry
Berchuck, Jacob E.
Szallasi, Zoltan
Choueiri, Toni K.
Freedman, Matthew L.
author_sort Baca, Sylvan C.
collection PubMed
description 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.
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spelling pubmed-106958302023-12-06 Liquid biopsy epigenomic profiling for cancer subtyping Baca, Sylvan C. Seo, Ji-Heui Davidsohn, Matthew P. Fortunato, Brad Semaan, Karl Sotudian, Shahabbedin Lakshminarayanan, Gitanjali Diossy, Miklos Qiu, Xintao El Zarif, Talal Savignano, Hunter Canniff, John Madueke, Ikenna Saliby, Renee Maria Zhang, Ziwei Li, Rong Jiang, Yijia Taing, Len Awad, Mark Chau, Cindy H. DeCaprio, James A. Figg, William D. Greten, Tim F. Hata, Aaron N. Hodi, F. Stephen Hughes, Melissa E. Ligon, Keith L. Lin, Nancy Ng, Kimmie Oser, Matthew G. Meador, Catherine Parsons, Heather A. Pomerantz, Mark M. Rajan, Arun Ritz, Jerome Thakuria, Manisha Tolaney, Sara M. Wen, Patrick Y. Long, Henry Berchuck, Jacob E. Szallasi, Zoltan Choueiri, Toni K. Freedman, Matthew L. Nat Med Brief Communication 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. Nature Publishing Group US 2023-10-21 2023 /pmc/articles/PMC10695830/ /pubmed/37865722 http://dx.doi.org/10.1038/s41591-023-02605-z Text en © The Author(s) 2023, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Brief Communication
Baca, Sylvan C.
Seo, Ji-Heui
Davidsohn, Matthew P.
Fortunato, Brad
Semaan, Karl
Sotudian, Shahabbedin
Lakshminarayanan, Gitanjali
Diossy, Miklos
Qiu, Xintao
El Zarif, Talal
Savignano, Hunter
Canniff, John
Madueke, Ikenna
Saliby, Renee Maria
Zhang, Ziwei
Li, Rong
Jiang, Yijia
Taing, Len
Awad, Mark
Chau, Cindy H.
DeCaprio, James A.
Figg, William D.
Greten, Tim F.
Hata, Aaron N.
Hodi, F. Stephen
Hughes, Melissa E.
Ligon, Keith L.
Lin, Nancy
Ng, Kimmie
Oser, Matthew G.
Meador, Catherine
Parsons, Heather A.
Pomerantz, Mark M.
Rajan, Arun
Ritz, Jerome
Thakuria, Manisha
Tolaney, Sara M.
Wen, Patrick Y.
Long, Henry
Berchuck, Jacob E.
Szallasi, Zoltan
Choueiri, Toni K.
Freedman, Matthew L.
Liquid biopsy epigenomic profiling for cancer subtyping
title Liquid biopsy epigenomic profiling for cancer subtyping
title_full Liquid biopsy epigenomic profiling for cancer subtyping
title_fullStr Liquid biopsy epigenomic profiling for cancer subtyping
title_full_unstemmed Liquid biopsy epigenomic profiling for cancer subtyping
title_short Liquid biopsy epigenomic profiling for cancer subtyping
title_sort liquid biopsy epigenomic profiling for cancer subtyping
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10695830/
https://www.ncbi.nlm.nih.gov/pubmed/37865722
http://dx.doi.org/10.1038/s41591-023-02605-z
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