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. 2020 Mar 6;12(1):43.
doi: 10.1186/s13148-020-00831-7.

Genome-wide analysis of constitutional DNA methylation in familial melanoma

Catarina Salgado  1 , Nelleke Gruis  1 ; BIOS Consortium; Bastiaan T Heijmans  2 , Jan Oosting  3 , Remco van Doorn  4
Collaborators, Affiliations

Genome-wide analysis of constitutional DNA methylation in familial melanoma

Catarina Salgado et al. Clin Epigenetics. .

Abstract

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: DNA methylation; Epimutation; Familial melanoma; Loss of imprinting.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Methylation levels (β value) across the entire sequence of all established melanoma predisposition genes. In the upper part of each plot, the gene structure is represented in red and promoter region (“Promoter_associated” feature retrieved from Illumina annotation) in blue. The light grey arrow represents the transcription direction of the gene. For each CpG, the BIOS values are represented by the black vertical line with upper (average + 1 SD) and lower limits (average − 1SD). The families are represented as a X of different colours (family I—green, family II—blue, family III—yellow, family IV—light purple, family V—dark blue). To be considered as significantly different from the BIOS, the families’ symbols must go beyond the small black horizontal line (average ± 5.65 SD). Genes with more than 10 CpG sites assessed by 450K array were represented by 10 randomly selected CpGs. An extended version of figure 1 is available as supplementary information
Fig. 2
Fig. 2
Methylation levels (β value) in all 6 significant upregulated CpGs located in the promoter regions of the genes. In the upper part of each plot, the gene structure is represented in red and promoter region (“Promoter_associated” feature retrieved from Illumina annotation) in blue. The light grey arrow represents the transcription direction of the gene. For each CpG, the BIOS values are represented by the black vertical line with upper (average + 1 SD) and lower limits (average − 1SD). The families are represented as a X of different colours (family I—green, family II—blue, family III—yellow, family IV—light purple, family V—dark blue). To be considered as significantly different from the BIOS, the families’ symbols must go beyond the small black horizontal line (average ± 5.65 SD). Genes with more than 10 CpG sites assessed by 450K array were represented by 10 randomly selected CpGs. The upregulated CpG in each plot is aligned with a vertical light grey line, and in this case, the little horizontal lines become red since the families’ symbols exceeded these limits. An extended version of figure 2 is available as supplementary information
See this image and copyright information in PMC

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