학술논문
Genome-wide analysis of constitutional DNA methylation in familial melanoma
Document Type
Academic Journal
Author
Salgado, Catarina; Gruis, Nelleke; Bonder, Marc Jan; Luijk, René; Zhernakova, Dasha V.; Moed, Matthijs; Deelen, Patrick; Vermaat, Martijn; van Iterson, Maarten; van Dijk, Freerk; van Galen, Michiel; Bot, Jan; Jhamai, P. Mila; Verbiest, Michael; Suchiman, H. Eka D.; Verkerk, Marijn; van der Breggen, Ruud; van Rooij, Jeroen; Lakenberg, Nico; Arindrarto, Wibowo; Kielbasa, Szymon M.; van 't Hof, Peter; Nooren, Irene; Beekman, Marian; Deelen, Joris; van Heemst, Diana; Zhernakova, Alexandra; Tigchelaar, Ettje F.; Swertz, Morris A.; Hofman, Bert A.; Uitterlinden, André G.; Pool, René; van Dongen, Jenny; Hottenga, Jouke J.; Stehouwer, Coen D. A.; van der Kallen, Carla J. H.; Schalkwijk, Casper G.; van den Berg, Leonard H.; van Zwet, Erik W.; Mei, Hailiang; Slagboom, P. Eline; Wijmenga, Cisca; Veldink, Jan H.; van Greevenbroek, Marleen M. J.; van Duijn, Cornelia M.; Boomsma, Dorret I.; Isaacs, Aaron; Jansen, Rick; van Meurs, Joyce; 't Hoen, Peter A. C.; Franke, Lude
Source
Clinical Epigenetics. March 6, 2020, Vol. 12 Issue 1
Subject
Language
English
ISSN
1868-7075
Abstract
Author(s): Catarina Salgado[sup.1], Nelleke Gruis[sup.1], Marc Jan Bonder, René Luijk, Dasha V. Zhernakova, Matthijs Moed, Patrick Deelen, Martijn Vermaat, Maarten van Iterson, Freerk van Dijk, Michiel van Galen, Jan Bot, [...]
Background Heritable epigenetic alterations have been proposed as an explanation for familial clustering of melanoma. Here we performed genome-wide DNA methylation analysis on affected family members not carrying pathogenic variants in established melanoma susceptibility genes, compared with healthy volunteers. Results All melanoma susceptibility genes showed the absence of epimutations in familial melanoma patients, and no loss of imprinting was detected. Unbiased genome-wide DNA methylation analysis revealed significantly different levels of methylation in single CpG sites. The methylation level differences were small and did not affect reported tumour predisposition genes. Conclusion Our results provide no support for heritable epimutations as a cause of familial melanoma. Keywords: Epimutation, Loss of imprinting, DNA methylation, Familial melanoma
Background Heritable epigenetic alterations have been proposed as an explanation for familial clustering of melanoma. Here we performed genome-wide DNA methylation analysis on affected family members not carrying pathogenic variants in established melanoma susceptibility genes, compared with healthy volunteers. Results All melanoma susceptibility genes showed the absence of epimutations in familial melanoma patients, and no loss of imprinting was detected. Unbiased genome-wide DNA methylation analysis revealed significantly different levels of methylation in single CpG sites. The methylation level differences were small and did not affect reported tumour predisposition genes. Conclusion Our results provide no support for heritable epimutations as a cause of familial melanoma. Keywords: Epimutation, Loss of imprinting, DNA methylation, Familial melanoma