title: Genome-wide linkage scan for atypical nevi in p16-Leiden melanoma families.
abstract: In most Dutch melanoma families, a founder deletion in the melanoma susceptibility gene CDKN2A (which encodes p16) is present. This founder deletion (p16-Leiden) accounts for a significant proportion of the increased melanoma risk. However, it does not account for the Atypical Nevus (AN) phenotype that segregates in both p16-Leiden carriers and non-carriers. The AN-affected p16-Leiden family members are therefore a unique valuable resource for unraveling the genetic etiology of the AN phenotype, which is considered both a risk factor and a precursor lesion for melanoma. In this study, we performed a genome-wide scan for linkage in four p16-Leiden melanoma pedigrees, classifying family members with five or more AN as affected. The strongest evidence for an atypical nevus susceptibility gene was mapped to chromosome band 7q21.3 (two-point LOD score=2.751), a region containing candidate gene CDK6.
authors.affiliation: Departments of Human & Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. desnoo@lumc.nl
authors.forename: Femke A
authors.initials: FA
authors.lastname: de Snoo
authors.forename: Jouke-Jan
authors.initials: JJ
authors.lastname: Hottenga
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Gillanders
authors.forename: Loudewijk A
authors.initials: LA
authors.lastname: Sandkuijl
authors.forename: Mary Pat
authors.initials: MP
authors.lastname: Jones
authors.forename: Wilma
authors.initials: W
authors.lastname: Bergman
authors.forename: Clasine
authors.initials: C
authors.lastname: van der Drift
authors.forename: Inge
authors.initials: I
authors.lastname: van Leeuwen
authors.forename: Lenny
authors.initials: L
authors.lastname: van Mourik
authors.forename: Jeanet A C Ter
authors.initials: JA
authors.lastname: Huurne
authors.forename: Rune R
authors.initials: RR
authors.lastname: Frants
authors.forename: Rein
authors.initials: R
authors.lastname: Willemze
authors.forename: Martijn H
authors.initials: MH
authors.lastname: Breuning
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Trent
authors.forename: Nelleke A
authors.initials: NA
authors.lastname: Gruis
mesh_terms: D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics; D004416:Dysplastic Nevus Syndrome / Q000201:enzymology / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D017353:Gene Deletion; D019942:Genes, p16; D006580:Genetic Carrier Screening; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008545:Melanoma / Q000201:enzymology / Q000235:genetics*; D010375:Pedigree; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics*
chemical_list: C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6