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. Chau; James 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

doi:10.1038/s41591-023-02605-z

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 journal › Article › peer-review

24 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 language	English
Pages (from-to)	2737-2741
Number of pages	5
Journal	Nature Medicine
Volume	29
Issue number	11
DOIs	https://doi.org/10.1038/s41591-023-02605-z
State	Published - Nov 2023
Externally published	Yes

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Baca, S. C., Seo, J. H., Davidsohn, M. P., Fortunato, B., Semaan, K., Sotudian, S., Lakshminarayanan, G., Diossy, M., Qiu, X., El Zarif, T., Savignano, H., Canniff, J., Madueke, I., Saliby, R. M., Zhang, Z., Li, R., Jiang, Y., Taing, L., Awad, M., ... Freedman, M. L. (2023). Liquid biopsy epigenomic profiling for cancer subtyping. Nature Medicine, 29(11), 2737-2741. https://doi.org/10.1038/s41591-023-02605-z

@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 = "Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2023",

month = nov,

doi = "10.1038/s41591-023-02605-z",

language = "English",

volume = "29",

pages = "2737--2741",

journal = "Nature Medicine",

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Baca, SC, Seo, JH, Davidsohn, MP, Fortunato, B, Semaan, K, Sotudian, S, Lakshminarayanan, G, Diossy, M, Qiu, X, El Zarif, T, Savignano, H, Canniff, J, Madueke, I, Saliby, RM, Zhang, Z, Li, R, Jiang, Y, Taing, L, Awad, M, Chau, CH, DeCaprio, JA, Figg, WD, Greten, TF, Hata, AN, Hodi, FS, Hughes, ME, Ligon, KL, Lin, N, Ng, K, Oser, MG, Meador, C, Parsons, HA, Pomerantz, MM, Rajan, A, Ritz, J, Thakuria, M, Tolaney, SM, Wen, PY, Long, H, Berchuck, JE, Szallasi, Z, Choueiri, TK & Freedman, ML 2023, 'Liquid biopsy epigenomic profiling for cancer subtyping', Nature Medicine, vol. 29, no. 11, pp. 2737-2741. https://doi.org/10.1038/s41591-023-02605-z

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T1 - Liquid biopsy epigenomic profiling for cancer subtyping

AU - Baca, Sylvan C.

AU - Seo, Ji Heui

AU - Davidsohn, Matthew P.

AU - Fortunato, Brad

AU - Semaan, Karl

AU - Sotudian, Shahabbedin

AU - Lakshminarayanan, Gitanjali

AU - Diossy, Miklos

AU - Qiu, Xintao

AU - El Zarif, Talal

AU - Savignano, Hunter

AU - Canniff, John

AU - Madueke, Ikenna

AU - Saliby, Renee Maria

AU - Zhang, Ziwei

AU - Li, Rong

AU - Jiang, Yijia

AU - Taing, Len

AU - Awad, Mark

AU - Chau, Cindy H.

AU - DeCaprio, James A.

AU - Figg, William D.

AU - Greten, Tim F.

AU - Hata, Aaron N.

AU - Hodi, F. Stephen

AU - Hughes, Melissa E.

AU - Ligon, Keith L.

AU - Lin, Nancy

AU - Ng, Kimmie

AU - Oser, Matthew G.

AU - Meador, Catherine

AU - Parsons, Heather A.

AU - Pomerantz, Mark M.

AU - Rajan, Arun

AU - Ritz, Jerome

AU - Thakuria, Manisha

AU - Tolaney, Sara M.

AU - Wen, Patrick Y.

AU - Long, Henry

AU - Berchuck, Jacob E.

AU - Szallasi, Zoltan

AU - Choueiri, Toni K.

AU - Freedman, Matthew L.

PY - 2023/11

Y1 - 2023/11

N2 - 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.

AB - 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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U2 - 10.1038/s41591-023-02605-z

DO - 10.1038/s41591-023-02605-z

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AN - SCOPUS:85174611511

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SP - 2737

EP - 2741

JO - Nature Medicine

JF - Nature Medicine

IS - 11

ER -

Liquid biopsy epigenomic profiling for cancer subtyping

Abstract

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