Abstract

BACKGROUND: and several other genes have been shown to predispose to melanoma; however, the genetic basis of familial melanoma remains unknown in most cases. The objective of this study was to provide insight into the genetic basis of familial melanoma. METHODS: In order to identify novel melanoma susceptibility genes, whole exome sequencing (WES) analysis was applied in a Dutch family with melanoma. The causality of a candidate variant was characterised by performing cosegregation analysis in five affected family members using patient-derived tissues and digital droplet PCR analysis to accurately quantify mutant allele frequency. Functional in-vitro studies were performed to assess the pathogenicity of the candidate variant. RESULTS: p.Arg374Ter mutation results in strongly reduced expression of the truncated protein caused by proteasomal degradation. CONCLUSION: as a melanoma susceptibility gene.

Authors	Christodoulou, Eirini; van Doorn, Remco; Visser, Mijke; Teunisse, Amina; Versluis, Mieke; van der Velden, Pieter; Hayward, Nicholas K; Jochemsen, Aart; Gruis, Nelleke
Journal	JOURNAL OF MEDICAL GENETICS
Pages	203-210
Volume	57
Date	1/11/2019
Grant ID	641458
Funding Body	European Union
URL	http://www.ncbi.nlm.nih.gov/pubmed/?term=10.1136/jmedgenet-2019-106134