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    cfDNA methylome profiling for detection and subtyping of small cell lung cancers

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    Authors
    Chemi, Francesca
    Pearce, 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
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    Affiliation
    Nucleic Acid Biomarker Team, Cancer Biomarker Centre, Cancer Research UK Manchester Institute, University of Manchester, Alderley Edge, UK
    Issue Date
    2022
    
    Metadata
    Show full item record
    Abstract
    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 Cancer
    URI
    http://hdl.handle.net/10541/625557
    DOI
    10.1038/s43018-022-00415-9
    PubMed ID
    35941262
    Additional Links
    https://dx.doi.org/10.1038/s43018-022-00415-9
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1038/s43018-022-00415-9
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