Genome-wide analysis of constitutional DNA methylation in familial melanoma

Catarina Salgado; Nelleke Gruis; 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; P. Mila Jhamai; Michael Verbiest; H. Eka D. Suchiman; Marijn Verkerk; Ruud Van Der Breggen; Jeroen Van Rooij; Nico Lakenberg; Wibowo Arindrarto; Szymon M. Kielbasa; Peter Van 'T Hof; Irene Nooren; Marian Beekman; Joris Deelen; Diana Van Heemst; Alexandra Zhernakova; Ettje F. Tigchelaar; Morris A. Swertz; Bert A. Hofman; André G. Uitterlinden; René Pool; Jenny Van Dongen; Jouke J. Hottenga; Coen D.A. Stehouwer; Carla J.H. Van Der Kallen; Casper G. Schalkwijk; Leonard H. Van Den Berg; Erik W. Van Zwet; Hailiang Mei; P. Eline Slagboom; Cisca Wijmenga; Jan H. Veldink; Marleen M.J. Van Greevenbroek; Cornelia M. Van Duijn; Dorret I. Boomsma; Aaron Isaacs; Rick Jansen; Joyce Van Meurs; Peter A.C. Thoen; Lude Franke; Bastiaan T. Heijmans; Jan Oosting; Remco Van Doorn

doi:10.1186/s13148-020-00831-7

Genome-wide analysis of constitutional DNA methylation in familial melanoma

Catarina Salgado
, Nelleke Gruis
, 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
, P. Mila Jhamai
, Michael Verbiest
, H. Eka D. Suchiman
, Marijn Verkerk
, Ruud Van Der Breggen
, Jeroen Van Rooij
, Nico Lakenberg
, Wibowo Arindrarto

Szymon M. Kielbasa, Peter Van 'T Hof, Irene Nooren, Marian Beekman, Joris Deelen, Diana Van Heemst, Alexandra Zhernakova, Ettje F. Tigchelaar, Morris A. Swertz, Bert A. Hofman, André G. Uitterlinden, René Pool, Jenny Van Dongen, Jouke J. Hottenga, Coen D.A. Stehouwer, Carla J.H. Van Der Kallen, Casper G. Schalkwijk, Leonard H. Van Den Berg, Erik W. Van Zwet, Hailiang Mei, P. Eline Slagboom, Cisca Wijmenga, Jan H. Veldink, Marleen M.J. Van Greevenbroek, Cornelia M. Van Duijn, Dorret I. Boomsma, Aaron Isaacs, Rick Jansen, Joyce Van Meurs, Peter A.C. Thoen, Lude Franke, Bastiaan T. Heijmans, Jan Oosting, Remco Van Doorn^*

^*Corresponding author for this work

QBRI - Neurological Disorders Research Center

Leiden University

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

4 Citations (Scopus)

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
Journal	Clinical Epigenetics
Volume	12
Issue number	1
DOIs	https://doi.org/10.1186/s13148-020-00831-7
Publication status	Published - 6 Mar 2020

Keywords

DNA methylation
Epimutation
Familial melanoma
Loss of imprinting

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10.1186/s13148-020-00831-7

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Salgado, C., Gruis, N., Bonder, M. J., Luijk, R., Zhernakova, D. V., Moed, M., Deelen, P., Vermaat, M., Van Iterson, M., Van Dijk, F., Van Galen, M., Bot, J., Jhamai, P. M., Verbiest, M., Suchiman, H. E. D., Verkerk, M., Van Der Breggen, R., Van Rooij, J., Lakenberg, N., ... Van Doorn, R. (2020). Genome-wide analysis of constitutional DNA methylation in familial melanoma. Clinical Epigenetics, 12(1), Article 43. https://doi.org/10.1186/s13148-020-00831-7

@article{78eed05876694c9d97d6ed8b549b27cb,

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 = "DNA methylation, Epimutation, Familial melanoma, Loss of imprinting",

author = "Catarina Salgado and Nelleke Gruis and Bonder, \{Marc Jan\} and Ren{\'e} Luijk and Zhernakova, \{Dasha V.\} and Matthijs Moed and Patrick Deelen and Martijn Vermaat and \{Van Iterson\}, Maarten and \{Van Dijk\}, Freerk and \{Van Galen\}, Michiel and Jan Bot and Jhamai, \{P. Mila\} and Michael Verbiest and Suchiman, \{H. Eka D.\} and Marijn Verkerk and \{Van Der Breggen\}, Ruud and \{Van Rooij\}, Jeroen and Nico Lakenberg and Wibowo Arindrarto and Kielbasa, \{Szymon M.\} and \{Van 'T Hof\}, Peter and Irene Nooren and Marian Beekman and Joris Deelen and \{Van Heemst\}, Diana and Alexandra Zhernakova and Tigchelaar, \{Ettje F.\} and Swertz, \{Morris A.\} and Hofman, \{Bert A.\} and Uitterlinden, \{Andr{\'e} G.\} and Ren{\'e} Pool and \{Van Dongen\}, Jenny and Hottenga, \{Jouke J.\} and Stehouwer, \{Coen D.A.\} and \{Van Der Kallen\}, \{Carla J.H.\} and Schalkwijk, \{Casper G.\} and \{Van Den Berg\}, \{Leonard H.\} and \{Van Zwet\}, \{Erik W.\} and Hailiang Mei and Slagboom, \{P. Eline\} and Cisca Wijmenga and Veldink, \{Jan H.\} and \{Van Greevenbroek\}, \{Marleen M.J.\} and \{Van Duijn\}, \{Cornelia M.\} and Boomsma, \{Dorret I.\} and Aaron Isaacs and Rick Jansen and \{Van Meurs\}, Joyce and Thoen, \{Peter A.C.\} and Lude Franke and Heijmans, \{Bastiaan T.\} and Jan Oosting and \{Van Doorn\}, Remco",

note = "Publisher Copyright: {\textcopyright} 2020 The Author(s).",

year = "2020",

month = mar,

day = "6",

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

language = "English",

volume = "12",

journal = "Clinical Epigenetics",

issn = "1868-7075",

publisher = "BioMed Central Ltd",

number = "1",

}

Salgado, C, Gruis, N, Bonder, MJ, Luijk, R, Zhernakova, DV, Moed, M, Deelen, P, Vermaat, M, Van Iterson, M, Van Dijk, F, Van Galen, M, Bot, J, Jhamai, PM, Verbiest, M, Suchiman, HED, Verkerk, M, Van Der Breggen, R, Van Rooij, J, Lakenberg, N, Arindrarto, W, Kielbasa, SM, Van 'T Hof, P, Nooren, I, Beekman, M, Deelen, J, Van Heemst, D, Zhernakova, A, Tigchelaar, EF, Swertz, MA, Hofman, BA, Uitterlinden, AG, Pool, R, Van Dongen, J, Hottenga, JJ, Stehouwer, CDA, Van Der Kallen, CJH, Schalkwijk, CG, Van Den Berg, LH, Van Zwet, EW, Mei, H, Slagboom, PE, Wijmenga, C, Veldink, JH, Van Greevenbroek, MMJ, Van Duijn, CM, Boomsma, DI, Isaacs, A, Jansen, R, Van Meurs, J, Thoen, PAC, Franke, L, Heijmans, BT, Oosting, J & Van Doorn, R 2020, 'Genome-wide analysis of constitutional DNA methylation in familial melanoma', Clinical Epigenetics, vol. 12, no. 1, 43. https://doi.org/10.1186/s13148-020-00831-7

TY - JOUR

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

AU - Salgado, Catarina

AU - Gruis, Nelleke

AU - Bonder, Marc Jan

AU - Luijk, René

AU - Zhernakova, Dasha V.

AU - Moed, Matthijs

AU - Deelen, Patrick

AU - Vermaat, Martijn

AU - Van Iterson, Maarten

AU - Van Dijk, Freerk

AU - Van Galen, Michiel

AU - Bot, Jan

AU - Jhamai, P. Mila

AU - Verbiest, Michael

AU - Suchiman, H. Eka D.

AU - Verkerk, Marijn

AU - Van Der Breggen, Ruud

AU - Van Rooij, Jeroen

AU - Lakenberg, Nico

AU - Arindrarto, Wibowo

AU - Kielbasa, Szymon M.

AU - Van 'T Hof, Peter

AU - Nooren, Irene

AU - Beekman, Marian

AU - Deelen, Joris

AU - Van Heemst, Diana

AU - Zhernakova, Alexandra

AU - Tigchelaar, Ettje F.

AU - Swertz, Morris A.

AU - Hofman, Bert A.

AU - Uitterlinden, André G.

AU - Pool, René

AU - Van Dongen, Jenny

AU - Hottenga, Jouke J.

AU - Stehouwer, Coen D.A.

AU - Van Der Kallen, Carla J.H.

AU - Schalkwijk, Casper G.

AU - Van Den Berg, Leonard H.

AU - Van Zwet, Erik W.

AU - Mei, Hailiang

AU - Slagboom, P. Eline

AU - Wijmenga, Cisca

AU - Veldink, Jan H.

AU - Van Greevenbroek, Marleen M.J.

AU - Van Duijn, Cornelia M.

AU - Boomsma, Dorret I.

AU - Isaacs, Aaron

AU - Jansen, Rick

AU - Van Meurs, Joyce

AU - Thoen, Peter A.C.

AU - Franke, Lude

AU - Heijmans, Bastiaan T.

AU - Oosting, Jan

AU - Van Doorn, Remco

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 - DNA methylation

KW - Epimutation

KW - Familial melanoma

KW - Loss of imprinting

UR - https://www.scopus.com/pages/publications/85081258657

U2 - 10.1186/s13148-020-00831-7

DO - 10.1186/s13148-020-00831-7

M3 - Article

C2 - 32143689

AN - SCOPUS:85081258657

SN - 1868-7075

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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