Genome-wide linkage scan for atypical nevi in p16-Leiden melanoma families.
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.
de Snoo
Femke A
FA
Departments of Human & Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. desnoo@lumc.nl
Hottenga
Jouke-Jan
JJ
Gillanders
Elizabeth M
EM
Sandkuijl
Loudewijk A
LA
Jones
Mary Pat
MP
Bergman
Wilma
W
van der Drift
Clasine
C
van Leeuwen
Inge
I
van Mourik
Lenny
L
Huurne
Jeanet A C Ter
JA
Frants
Rune R
RR
Willemze
Rein
R
Breuning
Martijn H
MH
Trent
Jeffrey M
JM
Gruis
Nelleke A
NA
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*
C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6