Differentially methylated regions within lung cancer risk loci are enriched in deregulated enhancers

Genome-wide association studies (GWAS) have identified SNPs linked with lung cancer risk. Our aim was to discover the genes, non-coding RNAs, and regulatory elements within GWAS-identified risk regions that are deregulated in non-small cell lung carcinoma (NSCLC) to identify novel, clinically target...

Descripción completa

Detalles Bibliográficos
Autores: Laplana Lafaja, Marina, Bieg, Matthias, Faltus, Christian, Melnik, Svitlana, Bogatyrova, Olga, Gu, Zuguang, Muley, Thomas, Meister, Michael, Dienemann, Hendrik C., Herpel, Esther, Amos, Christopher I., Schlesner, Matthias, Eils, Roland, Plass, Christoph, Risch, Angela
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universitat de Lleida (UdL)
Repositorio:Repositori Obert UdL
OAI Identifier:oai:repositori.udl.cat:10459.1/70710
Acceso en línea:https://doi.org/10.1080/15592294.2021.1878723
http://hdl.handle.net/10459.1/70710
Access Level:acceso abierto
Palabra clave:Risk SNPs
Bisulphite sequencing
DNA methylation
Enhancers
Lung cancer
DMR
id ES_ec082e851d8c4b77ab0bf04d3cb154cd
oai_identifier_str oai:repositori.udl.cat:10459.1/70710
network_acronym_str ES
network_name_str España
repository_id_str
spelling Differentially methylated regions within lung cancer risk loci are enriched in deregulated enhancersLaplana Lafaja, MarinaBieg, MatthiasFaltus, ChristianMelnik, SvitlanaBogatyrova, OlgaGu, ZuguangMuley, ThomasMeister, MichaelDienemann, Hendrik C.Herpel, EstherAmos, Christopher I.Schlesner, MatthiasEils, RolandPlass, ChristophRisch, AngelaRisk SNPsBisulphite sequencingDNA methylationEnhancersLung cancerDMRGenome-wide association studies (GWAS) have identified SNPs linked with lung cancer risk. Our aim was to discover the genes, non-coding RNAs, and regulatory elements within GWAS-identified risk regions that are deregulated in non-small cell lung carcinoma (NSCLC) to identify novel, clinically targetable genes and mechanisms in carcinogenesis. A targeted bisulphite-sequencing approach was used to comprehensively investigate DNA methylation changes occurring within lung cancer risk regions in 17 NSCLC and adjacent normal tissue pairs. We report differences in differentially methylated regions between adenocarcinoma and squamous cell carcinoma. Among the minimal regions found to be differentially methylated in at least 50% of the patients, 7 candidates were replicated in 2 independent cohorts (n = 27 and n = 87) and the potential of 6 as methylation-dependent regulatory elements was confirmed by functional assays. This study contributes to understanding the pathways implicated in lung cancer initiation and progression, and provides new potential targets for cancer treatment.This work was supported by the Deutsche Krebshilfe [70-2387; 70-2919, 106910]; National Institutes of Health [CA148127]; Deutsches Zentrum für Lungenforschung (DZL).Taylor & Francis2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://doi.org/10.1080/15592294.2021.1878723http://hdl.handle.net/10459.1/70710reponame:Repositori Obert UdL instname:Universitat de Lleida (UdL)InglésReproducció del document publicat a: https://doi.org/10.1080/15592294.2021.1878723Epigenetics, 2022, vol. 17, núm. 2, p. 117–132cc-by-nc-nd (c) Laplana et al., 2021info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-nd/4.0/oai:repositori.udl.cat:10459.1/707102026-06-24T12:42:17Z
dc.title.none.fl_str_mv Differentially methylated regions within lung cancer risk loci are enriched in deregulated enhancers
title Differentially methylated regions within lung cancer risk loci are enriched in deregulated enhancers
spellingShingle Differentially methylated regions within lung cancer risk loci are enriched in deregulated enhancers
Laplana Lafaja, Marina
Risk SNPs
Bisulphite sequencing
DNA methylation
Enhancers
Lung cancer
DMR
title_short Differentially methylated regions within lung cancer risk loci are enriched in deregulated enhancers
title_full Differentially methylated regions within lung cancer risk loci are enriched in deregulated enhancers
title_fullStr Differentially methylated regions within lung cancer risk loci are enriched in deregulated enhancers
title_full_unstemmed Differentially methylated regions within lung cancer risk loci are enriched in deregulated enhancers
title_sort Differentially methylated regions within lung cancer risk loci are enriched in deregulated enhancers
dc.creator.none.fl_str_mv Laplana Lafaja, Marina
Bieg, Matthias
Faltus, Christian
Melnik, Svitlana
Bogatyrova, Olga
Gu, Zuguang
Muley, Thomas
Meister, Michael
Dienemann, Hendrik C.
Herpel, Esther
Amos, Christopher I.
Schlesner, Matthias
Eils, Roland
Plass, Christoph
Risch, Angela
author Laplana Lafaja, Marina
author_facet Laplana Lafaja, Marina
Bieg, Matthias
Faltus, Christian
Melnik, Svitlana
Bogatyrova, Olga
Gu, Zuguang
Muley, Thomas
Meister, Michael
Dienemann, Hendrik C.
Herpel, Esther
Amos, Christopher I.
Schlesner, Matthias
Eils, Roland
Plass, Christoph
Risch, Angela
author_role author
author2 Bieg, Matthias
Faltus, Christian
Melnik, Svitlana
Bogatyrova, Olga
Gu, Zuguang
Muley, Thomas
Meister, Michael
Dienemann, Hendrik C.
Herpel, Esther
Amos, Christopher I.
Schlesner, Matthias
Eils, Roland
Plass, Christoph
Risch, Angela
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Risk SNPs
Bisulphite sequencing
DNA methylation
Enhancers
Lung cancer
DMR
topic Risk SNPs
Bisulphite sequencing
DNA methylation
Enhancers
Lung cancer
DMR
description Genome-wide association studies (GWAS) have identified SNPs linked with lung cancer risk. Our aim was to discover the genes, non-coding RNAs, and regulatory elements within GWAS-identified risk regions that are deregulated in non-small cell lung carcinoma (NSCLC) to identify novel, clinically targetable genes and mechanisms in carcinogenesis. A targeted bisulphite-sequencing approach was used to comprehensively investigate DNA methylation changes occurring within lung cancer risk regions in 17 NSCLC and adjacent normal tissue pairs. We report differences in differentially methylated regions between adenocarcinoma and squamous cell carcinoma. Among the minimal regions found to be differentially methylated in at least 50% of the patients, 7 candidates were replicated in 2 independent cohorts (n = 27 and n = 87) and the potential of 6 as methylation-dependent regulatory elements was confirmed by functional assays. This study contributes to understanding the pathways implicated in lung cancer initiation and progression, and provides new potential targets for cancer treatment.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.1080/15592294.2021.1878723
http://hdl.handle.net/10459.1/70710
url https://doi.org/10.1080/15592294.2021.1878723
http://hdl.handle.net/10459.1/70710
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1080/15592294.2021.1878723
Epigenetics, 2022, vol. 17, núm. 2, p. 117–132
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Laplana et al., 2021
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
rights_invalid_str_mv cc-by-nc-nd (c) Laplana et al., 2021
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Taylor & Francis
publisher.none.fl_str_mv Taylor & Francis
dc.source.none.fl_str_mv reponame:Repositori Obert UdL
instname:Universitat de Lleida (UdL)
instname_str Universitat de Lleida (UdL)
reponame_str Repositori Obert UdL
collection Repositori Obert UdL
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869423280116465664
score 15.812429

Similares en LA Referencia