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cfDNA methylome profiling for detection and subtyping of small cell lung cancers
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
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
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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.
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
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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Date
2022
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Article
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.