cfDNA methylome profiling for detection and subtyping of small cell lung cancers.
Journal
Nature cancer
ISSN: 2662-1347
Titre abrégé: Nat Cancer
Pays: England
ID NLM: 101761119
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
received:
31
01
2022
accepted:
28
06
2022
pubmed:
9
8
2022
medline:
26
10
2022
entrez:
8
8
2022
Statut:
ppublish
Résumé
Small cell lung cancer (SCLC) is characterized by morphologic, epigenetic and transcriptomic heterogeneity. Subtypes based upon predominant transcription factor expression have been defined that, in mouse models and cell lines, exhibit potential differential therapeutic vulnerabilities, with epigenetically distinct SCLC subtypes also described. The clinical relevance of these subtypes is unclear, due in part to challenges in obtaining tumor biopsies for reliable profiling. Here we describe a robust workflow for genome-wide DNA methylation profiling applied to both patient-derived models and to patients' circulating cell-free DNA (cfDNA). Tumor-specific methylation patterns were readily detected in cfDNA samples from patients with SCLC and were correlated with survival outcomes. cfDNA methylation also discriminated between the transcription factor SCLC subtypes, a precedent for a liquid biopsy cfDNA-methylation approach to molecularly subtype SCLC. Our data reveal the potential clinical utility of cfDNA methylation profiling as a universally applicable liquid biopsy approach for the sensitive detection, monitoring and molecular subtyping of patients with SCLC.
Identifiants
pubmed: 35941262
doi: 10.1038/s43018-022-00415-9
pii: 10.1038/s43018-022-00415-9
pmc: PMC9586870
doi:
Substances chimiques
Cell-Free Nucleic Acids
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1260-1270Subventions
Organisme : NCI NIH HHS
ID : R35 CA263816
Pays : United States
Organisme : Department of Health
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA213274
Pays : United States
Organisme : Cancer Research UK
ID : C5759/A27412
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R01 CA197936
Pays : United States
Organisme : Cancer Research UK
ID : A25254
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A20465
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A25146
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
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