Cell Rep. 2014 Apr 2. pii: S2211-1247(14)00194-6. doi: 10.1016/j.celrep.2014.03.016. [Epub ahead of print]
Linkage of DNA Methylation Quantitative Trait Loci to Human Cancer Risk.
Heyn H1, Sayols S2, Moutinho C2, Vidal E2, Sanchez-Mut JV2, Stefansson OA2, Nadal E3, Moran S2, Eyfjord JE4, Gonzalez-Suarez E2, Pujana MA5, Esteller M6.
Epigenetic regulation and, in particular, DNA methylation have been linked to the underlying genetic sequence. DNA methylation quantitative trait loci (meQTL) have been identified through significant associations between the genetic and epigenetic codes in physiological and pathological contexts. We propose that interrogating the interplay between polymorphic alleles and DNA methylation is a powerful method for improving our interpretation of risk alleles identified in genome-wide association studies that otherwise lack mechanistic explanation. We integrated patient cancer risk genotype data and genome-scale DNA methylation profiles of 3,649 primary human tumors, representing 13 solid cancer types. We provide a comprehensive meQTL catalog containing DNA methylation associations for 21% of interrogated cancer risk polymorphisms. Differentially methylated loci harbor previously reported and as-yet-unidentified cancer genes. We suggest that such regulation at the DNA level can provide a considerable amount of new information about the biology of cancer-risk alleles.
Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
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