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.

中文翻译：

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家族性黑色素瘤中结构性 DNA 甲基化的全基因组分析。

背景已提出可遗传的表观遗传改变作为黑色素瘤家族聚集的解释。在这里，我们对与健康志愿者相比，在已建立的黑色素瘤易感基因中不携带致病变异的受影响家庭成员进行了全基因组 DNA 甲基化分析。结果所有黑色素瘤易感基因在家族性黑色素瘤患者中均未发生表观突变，未检测到印迹丢失。无偏见的全基因组 DNA 甲基化分析揭示了单个 CpG 位点的甲基化水平显着不同。甲基化水平差异很小，不影响报告的肿瘤易感基因。结论我们的结果不支持可遗传的表观突变是家族性黑色素瘤的一个原因。