Genome-wide analysis of constitutional DNA methylation in familial melanoma

Catarina Salgado; Nelleke Gruis; Bastiaan T Heijmans; Jan Oosting; Remco van Doorn; BIOS Consortium; Aaron Isaacs

doi:10.1186/s13148-020-00831-7

Genome-wide analysis of constitutional DNA methylation in familial melanoma

Catarina Salgado, Nelleke Gruis, Bastiaan T Heijmans, Jan Oosting, Remco van Doorn^*, BIOS Consortium, Aaron Isaacs

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	43
Number of pages	7
Journal	Clinical epigenetics
Volume	12
Issue number	1
DOIs	https://doi.org/10.1186/s13148-020-00831-7
Publication status	Published - 6 Mar 2020
Externally published	Yes

Keywords

CDKN2A
DNA methylation
Epimutation
Familial melanoma
GENE
GERMLINE EPIMUTATION
INHERITANCE
Loss of imprinting
MLH1
MSH2
MUTATIONS
VARIANT

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title = "Genome-wide analysis of constitutional DNA methylation in familial melanoma",

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 = "CDKN2A, DNA methylation, Epimutation, Familial melanoma, GENE, GERMLINE EPIMUTATION, INHERITANCE, Loss of imprinting, MLH1, MSH2, MUTATIONS, VARIANT",

author = "Catarina Salgado and Nelleke Gruis and Heijmans, \{Bastiaan T\} and Jan Oosting and \{van Doorn\}, Remco and \{BIOS Consortium\} and Aaron Isaacs",

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year = "2020",

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doi = "10.1186/s13148-020-00831-7",

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journal = "Clinical epigenetics",

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T1 - Genome-wide analysis of constitutional DNA methylation in familial melanoma

AU - Salgado, Catarina

AU - Gruis, Nelleke

AU - Heijmans, Bastiaan T

AU - Oosting, Jan

AU - van Doorn, Remco

AU - BIOS Consortium

AU - Isaacs, Aaron

PY - 2020/3/6

Y1 - 2020/3/6

N2 - 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.

AB - 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.

KW - CDKN2A

KW - DNA methylation

KW - Epimutation

KW - Familial melanoma

KW - GENE

KW - GERMLINE EPIMUTATION

KW - INHERITANCE

KW - Loss of imprinting

KW - MLH1

KW - MSH2

KW - MUTATIONS

KW - VARIANT

U2 - 10.1186/s13148-020-00831-7

DO - 10.1186/s13148-020-00831-7

M3 - Article

C2 - 32143689

SN - 1868-7083

VL - 12

JO - Clinical epigenetics

JF - Clinical epigenetics

IS - 1

M1 - 43

ER -

Genome-wide analysis of constitutional DNA methylation in familial melanoma

Abstract

Keywords

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