Differentially methylated regions within lung cancer risk loci are enriched in deregulated enhancers.
DMR
DNA methylation
Risk SNPs
bisulphite sequencing
enhancers
lung cancer
Journal
Epigenetics
ISSN: 1559-2308
Titre abrégé: Epigenetics
Pays: United States
ID NLM: 101265293
Informations de publication
Date de publication:
Historique:
pubmed:
18
2
2021
medline:
2
4
2022
entrez:
17
2
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33595421
doi: 10.1080/15592294.2021.1878723
pmc: PMC8865272
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
117-132Subventions
Organisme : NCI NIH HHS
ID : U19 CA148127
Pays : United States
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