Liquid biopsy epigenomic profiling for cancer subtyping.


Journal

Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015

Informations de publication

Date de publication:
Nov 2023
Historique:
received: 15 07 2023
accepted: 21 09 2023
medline: 27 11 2023
pubmed: 22 10 2023
entrez: 21 10 2023
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 37865722
doi: 10.1038/s41591-023-02605-z
pii: 10.1038/s41591-023-02605-z
pmc: PMC10695830
doi:

Substances chimiques

Biomarkers, Tumor 0
Circulating Tumor DNA 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2737-2741

Subventions

Organisme : NCI NIH HHS
ID : P01 CA228696
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA137008
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA156732
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA156734
Pays : United States

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.

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Auteurs

Sylvan C Baca (SC)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.
Eli and Edythe L. Broad Institute, Cambridge, MA, USA.

Ji-Heui Seo (JH)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.

Matthew P Davidsohn (MP)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.

Brad Fortunato (B)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.
Eli and Edythe L. Broad Institute, Cambridge, MA, USA.

Karl Semaan (K)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Eli and Edythe L. Broad Institute, Cambridge, MA, USA.

Shahabbedin Sotudian (S)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.
Eli and Edythe L. Broad Institute, Cambridge, MA, USA.

Gitanjali Lakshminarayanan (G)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.

Miklos Diossy (M)

Computational Health Informatics Program, Boston Children's Hospital, Boston, MA, USA.

Xintao Qiu (X)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.

Talal El Zarif (T)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.

Hunter Savignano (H)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.

John Canniff (J)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.

Ikenna Madueke (I)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.

Renee Maria Saliby (RM)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.

Ziwei Zhang (Z)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.
Eli and Edythe L. Broad Institute, Cambridge, MA, USA.

Rong Li (R)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.

Yijia Jiang (Y)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.

Len Taing (L)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.

Mark Awad (M)

Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Cindy H Chau (CH)

Molecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

James A DeCaprio (JA)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

William D Figg (WD)

Molecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Tim F Greten (TF)

Liver Cancer Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Aaron N Hata (AN)

Massachusetts General Hospital Cancer Center, Boston, MA, USA.
Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

F Stephen Hodi (FS)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Melissa E Hughes (ME)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Keith L Ligon (KL)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.

Nancy Lin (N)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Kimmie Ng (K)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Matthew G Oser (MG)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Catherine Meador (C)

Massachusetts General Hospital Cancer Center, Boston, MA, USA.
Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Heather A Parsons (HA)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Mark M Pomerantz (MM)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.

Arun Rajan (A)

Thoracic and Gastrointestinal Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, MD, USA.

Jerome Ritz (J)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Manisha Thakuria (M)

Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Center for Cutaneous Oncology, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA.

Sara M Tolaney (SM)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Patrick Y Wen (PY)

Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Henry Long (H)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.

Jacob E Berchuck (JE)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.

Zoltan Szallasi (Z)

Computational Health Informatics Program, Boston Children's Hospital, Boston, MA, USA.
Danish Cancer Institute, Copenhagen, Denmark.
Department of Bioinformatics and Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary.

Toni K Choueiri (TK)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Matthew L Freedman (ML)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. matthew_freedman@dfci.harvard.edu.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA. matthew_freedman@dfci.harvard.edu.
Eli and Edythe L. Broad Institute, Cambridge, MA, USA. matthew_freedman@dfci.harvard.edu.

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