Genome-wide analysis of constitutional DNA methylation in familial melanoma.
Salgado C., Gruis N., BIOS Consortium None., Heijmans BT., Oosting J., van Doorn R.
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.