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Multigene panel sequencing of established and candidate melanoma susceptibility genes in a large cohort of Dutch non-CDKN2A/CDK4 melanoma families. / Dutch Working Group for Clinical Oncogenetics; Potjer, Thomas P; Bollen, Sander; Grimbergen, Anneliese J E M; van Doorn, Remco; Gruis, Nelleke A; van Asperen, Christi J; Hes, Frederik J; van der Stoep, Nienke.

In: International Journal of Cancer, Vol. 144, No. 10, 15.05.2019, p. 2453-2464.

Research output: Contribution to journalArticleResearchpeer-review

Harvard

Dutch Working Group for Clinical Oncogenetics, Potjer, TP, Bollen, S, Grimbergen, AJEM, van Doorn, R, Gruis, NA, van Asperen, CJ, Hes, FJ & van der Stoep, N 2019, 'Multigene panel sequencing of established and candidate melanoma susceptibility genes in a large cohort of Dutch non-CDKN2A/CDK4 melanoma families' International Journal of Cancer, vol. 144, no. 10, pp. 2453-2464. https://doi.org/10.1002/ijc.31984

APA

Dutch Working Group for Clinical Oncogenetics, Potjer, T. P., Bollen, S., Grimbergen, A. J. E. M., van Doorn, R., Gruis, N. A., ... van der Stoep, N. (2019). Multigene panel sequencing of established and candidate melanoma susceptibility genes in a large cohort of Dutch non-CDKN2A/CDK4 melanoma families. International Journal of Cancer, 144(10), 2453-2464. https://doi.org/10.1002/ijc.31984

Vancouver

Dutch Working Group for Clinical Oncogenetics, Potjer TP, Bollen S, Grimbergen AJEM, van Doorn R, Gruis NA et al. Multigene panel sequencing of established and candidate melanoma susceptibility genes in a large cohort of Dutch non-CDKN2A/CDK4 melanoma families. International Journal of Cancer. 2019 May 15;144(10):2453-2464. https://doi.org/10.1002/ijc.31984

Author

Dutch Working Group for Clinical Oncogenetics ; Potjer, Thomas P ; Bollen, Sander ; Grimbergen, Anneliese J E M ; van Doorn, Remco ; Gruis, Nelleke A ; van Asperen, Christi J ; Hes, Frederik J ; van der Stoep, Nienke. / Multigene panel sequencing of established and candidate melanoma susceptibility genes in a large cohort of Dutch non-CDKN2A/CDK4 melanoma families. In: International Journal of Cancer. 2019 ; Vol. 144, No. 10. pp. 2453-2464.

BibTeX

@article{2f59317cc90a4833a38aef8f756aefee,
title = "Multigene panel sequencing of established and candidate melanoma susceptibility genes in a large cohort of Dutch non-CDKN2A/CDK4 melanoma families",
abstract = "Germline mutations in the major melanoma susceptibility gene CDKN2A explain genetic predisposition in only 10-40{\%} of melanoma-prone families. In our study we comprehensively characterized 488 melanoma cases from 451 non-CDKN2A/CDK4 families for mutations in 30 established and candidate melanoma susceptibility genes using a custom-designed targeted gene panel approach. We identified (likely) pathogenic variants in established melanoma susceptibility genes in 18 families (n = 3 BAP1, n = 15 MITF p.E318K; diagnostic yield 4.0{\%}). Among the three identified BAP1-families, there were no reported diagnoses of uveal melanoma or malignant mesothelioma. We additionally identified two potentially deleterious missense variants in the telomere maintenance genes ACD and TERF2IP, but none in the POT1 gene. MC1R risk variants were strongly enriched in our familial melanoma cohort compared to healthy controls (R variants: OR 3.67, 95{\%} CI 2.88-4.68, p < 0.001). Several variants of interest were also identified in candidate melanoma susceptibility genes, in particular rare (pathogenic) variants in the albinism gene OCA2 were repeatedly found. We conclude that multigene panel testing for familial melanoma is appropriate considering the additional 4{\%} diagnostic yield in non-CDKN2A/CDK4 families. Our study shows that BAP1 and MITF are important genes to be included in such a diagnostic test.",
keywords = "BAP1, MITF, OCA2, candidate susceptibility genes, familial melanoma, gene panel sequencing, genetic susceptibility, high-penetrance genes",
author = "{Dutch Working Group for Clinical Oncogenetics} and Potjer, {Thomas P} and Sander Bollen and Grimbergen, {Anneliese J E M} and {van Doorn}, Remco and Gruis, {Nelleke A} and {van Asperen}, {Christi J} and Hes, {Frederik J} and {van der Stoep}, Nienke",
note = "{\circledC} 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.",
year = "2019",
month = "5",
day = "15",
doi = "10.1002/ijc.31984",
language = "English",
volume = "144",
pages = "2453--2464",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "Wiley-Liss Inc.",
number = "10",

}

RIS

TY - JOUR

T1 - Multigene panel sequencing of established and candidate melanoma susceptibility genes in a large cohort of Dutch non-CDKN2A/CDK4 melanoma families

AU - Dutch Working Group for Clinical Oncogenetics

AU - Potjer, Thomas P

AU - Bollen, Sander

AU - Grimbergen, Anneliese J E M

AU - van Doorn, Remco

AU - Gruis, Nelleke A

AU - van Asperen, Christi J

AU - Hes, Frederik J

AU - van der Stoep, Nienke

N1 - © 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

PY - 2019/5/15

Y1 - 2019/5/15

N2 - Germline mutations in the major melanoma susceptibility gene CDKN2A explain genetic predisposition in only 10-40% of melanoma-prone families. In our study we comprehensively characterized 488 melanoma cases from 451 non-CDKN2A/CDK4 families for mutations in 30 established and candidate melanoma susceptibility genes using a custom-designed targeted gene panel approach. We identified (likely) pathogenic variants in established melanoma susceptibility genes in 18 families (n = 3 BAP1, n = 15 MITF p.E318K; diagnostic yield 4.0%). Among the three identified BAP1-families, there were no reported diagnoses of uveal melanoma or malignant mesothelioma. We additionally identified two potentially deleterious missense variants in the telomere maintenance genes ACD and TERF2IP, but none in the POT1 gene. MC1R risk variants were strongly enriched in our familial melanoma cohort compared to healthy controls (R variants: OR 3.67, 95% CI 2.88-4.68, p < 0.001). Several variants of interest were also identified in candidate melanoma susceptibility genes, in particular rare (pathogenic) variants in the albinism gene OCA2 were repeatedly found. We conclude that multigene panel testing for familial melanoma is appropriate considering the additional 4% diagnostic yield in non-CDKN2A/CDK4 families. Our study shows that BAP1 and MITF are important genes to be included in such a diagnostic test.

AB - Germline mutations in the major melanoma susceptibility gene CDKN2A explain genetic predisposition in only 10-40% of melanoma-prone families. In our study we comprehensively characterized 488 melanoma cases from 451 non-CDKN2A/CDK4 families for mutations in 30 established and candidate melanoma susceptibility genes using a custom-designed targeted gene panel approach. We identified (likely) pathogenic variants in established melanoma susceptibility genes in 18 families (n = 3 BAP1, n = 15 MITF p.E318K; diagnostic yield 4.0%). Among the three identified BAP1-families, there were no reported diagnoses of uveal melanoma or malignant mesothelioma. We additionally identified two potentially deleterious missense variants in the telomere maintenance genes ACD and TERF2IP, but none in the POT1 gene. MC1R risk variants were strongly enriched in our familial melanoma cohort compared to healthy controls (R variants: OR 3.67, 95% CI 2.88-4.68, p < 0.001). Several variants of interest were also identified in candidate melanoma susceptibility genes, in particular rare (pathogenic) variants in the albinism gene OCA2 were repeatedly found. We conclude that multigene panel testing for familial melanoma is appropriate considering the additional 4% diagnostic yield in non-CDKN2A/CDK4 families. Our study shows that BAP1 and MITF are important genes to be included in such a diagnostic test.

KW - BAP1

KW - MITF

KW - OCA2

KW - candidate susceptibility genes

KW - familial melanoma

KW - gene panel sequencing

KW - genetic susceptibility

KW - high-penetrance genes

U2 - 10.1002/ijc.31984

DO - 10.1002/ijc.31984

M3 - Article

VL - 144

SP - 2453

EP - 2464

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 10

ER -

ID: 44276964