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

Francesca Chemi; Simon Pearce; Alexandra Clipson; Steven Hill; Alicia-Marie Conway; Sophie Alice Richardson; K Kamieniecka; R Caeser; Daniel White; S Mohan; V Foy; Kathryn Simpson; M Galvin; KK Frese; Lynsey Priest; J Egger; Alastair Kerr; PP Massion; John Poirier; Gerard Brady; F Blackhall; Dominic Rothwell; Charles Rudin; Caroline Dive

doi:10.1038/s43018-022-00415-9

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

Francesca Chemi, Simon Pearce, Alexandra Clipson, Steven Hill, Alicia-Marie Conway, Sophie Alice Richardson, K Kamieniecka, R Caeser, Daniel White, S Mohan, V Foy, Kathryn Simpson, M Galvin, KK Frese, Lynsey Priest, J Egger, Alastair Kerr, PP Massion, John Poirier, Gerard BradyF Blackhall, Dominic Rothwell, Charles Rudin, Caroline Dive

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1260-1270
Number of pages	11
Journal	Nature Cancer
Volume	3
Issue number	10
Early online date	8 Aug 2022
DOIs	https://doi.org/10.1038/s43018-022-00415-9
Publication status	Published - 1 Oct 2022

Keywords

Animals
Cell-Free Nucleic Acids/genetics
DNA Methylation/genetics
Epigenome/genetics
Lung Neoplasms/diagnosis
Mice
Small Cell Lung Carcinoma/diagnosis
Transcription Factors/genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s43018-022-00415-9

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Chemi, F., Pearce, S., Clipson, A., Hill, S., Conway, A.-M., Richardson, S. A., Kamieniecka, K., Caeser, R., White, D., Mohan, S., Foy, V., Simpson, K., Galvin, M., Frese, KK., Priest, L., Egger, J., Kerr, A., Massion, PP., Poirier, J., ... Dive, C. (2022). cfDNA methylome profiling for detection and subtyping of small cell lung cancers. Nature Cancer, 3(10), 1260-1270. https://doi.org/10.1038/s43018-022-00415-9

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title = "cfDNA methylome profiling for detection and subtyping of small cell lung cancers.",

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.",

keywords = "Animals, Cell-Free Nucleic Acids/genetics, DNA Methylation/genetics, Epigenome/genetics, Lung Neoplasms/diagnosis, Mice, Small Cell Lung Carcinoma/diagnosis, Transcription Factors/genetics",

author = "Francesca Chemi and Simon Pearce and Alexandra Clipson and Steven Hill and Alicia-Marie Conway and Richardson, {Sophie Alice} and K Kamieniecka and R Caeser and Daniel White and S Mohan and V Foy and Kathryn Simpson and M Galvin and KK Frese and Lynsey Priest and J Egger and Alastair Kerr and PP Massion and John Poirier and Gerard Brady and F Blackhall and Dominic Rothwell and Charles Rudin and Caroline Dive",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = oct,

day = "1",

doi = "10.1038/s43018-022-00415-9",

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Chemi, F, Pearce, S, Clipson, A, Hill, S, Conway, A-M , Richardson, SA, Kamieniecka, K, Caeser, R, White, D, Mohan, S, Foy, V, Simpson, K, Galvin, M, Frese, KK, Priest, L, Egger, J, Kerr, A, Massion, PP, Poirier, J, Brady, G, Blackhall, F, Rothwell, D, Rudin, C & Dive, C 2022, 'cfDNA methylome profiling for detection and subtyping of small cell lung cancers.', Nature Cancer, vol. 3, no. 10, pp. 1260-1270. https://doi.org/10.1038/s43018-022-00415-9

TY - JOUR

T1 - cfDNA methylome profiling for detection and subtyping of small cell lung cancers.

AU - Chemi, Francesca

AU - Pearce, Simon

AU - Clipson, Alexandra

AU - Hill, Steven

AU - Conway, Alicia-Marie

AU - Richardson, Sophie Alice

AU - Kamieniecka, K

AU - Caeser, R

AU - White, Daniel

AU - Mohan, S

AU - Foy, V

AU - Simpson, Kathryn

AU - Galvin, M

AU - Frese, KK

AU - Priest, Lynsey

AU - Egger, J

AU - Kerr, Alastair

AU - Massion, PP

AU - Poirier, John

AU - Brady, Gerard

AU - Blackhall, F

AU - Rothwell, Dominic

AU - Rudin, Charles

AU - Dive, Caroline

PY - 2022/10/1

Y1 - 2022/10/1

N2 - 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.

AB - 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.

KW - Animals

KW - Cell-Free Nucleic Acids/genetics

KW - DNA Methylation/genetics

KW - Epigenome/genetics

KW - Lung Neoplasms/diagnosis

KW - Mice

KW - Small Cell Lung Carcinoma/diagnosis

KW - Transcription Factors/genetics

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UR - https://www.mendeley.com/catalogue/e42bf9d7-1ab0-3de9-9e98-ea83310d3909/

U2 - 10.1038/s43018-022-00415-9

DO - 10.1038/s43018-022-00415-9

M3 - Article

C2 - 35941262

SN - 2662-1347

VL - 3

SP - 1260

EP - 1270

JO - Nature Cancer

JF - Nature Cancer

IS - 10

ER -

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

Abstract

Keywords

UN SDGs

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