cfDNA methylome profiling for detection and subtyping of small cell lung cancers
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Authors
Chemi, FrancescaPearce, Simon P
Clipson, Alexandra
Hill, Steven M
Conway, Alicia-Marie
Richardson, Sophie A
Kamieniecka, Katarzyna
Caeser, R.
White, Daniel J
Mohan, Sumitra
Foy, Victoria
Simpson, Kathryn L
Galvin, Melanie
Frese, Kristopher K
Priest, Lynsey
Egger, J
Kerr, Alastair
Massion, P. P.
Poirier, John T
Brady, Ged
Blackhall, Fiona H
Rothwell, Dominic G
Rudin, C. M.
Dive, Caroline
Affiliation
Nucleic Acid Biomarker Team, Cancer Biomarker Centre, Cancer Research UK Manchester Institute, University of Manchester, Alderley Edge, UKIssue Date
2022
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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.Citation
Chemi F, Pearce SP, Clipson A, Hill SM, Conway AM, Richardson SA, et al. cfDNA methylome profiling for detection and subtyping of small cell lung cancers. Nat Cancer. 2022 Aug 8. PubMed PMID: 35941262. Epub 2022/08/09. eng.Journal
Nature CancerDOI
10.1038/s43018-022-00415-9PubMed ID
35941262Additional Links
https://dx.doi.org/10.1038/s43018-022-00415-9Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1038/s43018-022-00415-9
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