Genome-wide linkage scan for atypical nevi in p16-Leiden melanoma families

Eur J Hum Genet. 2008 Sep;16(9):1135-41. doi: 10.1038/ejhg.2008.72. Epub 2008 Apr 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Human, Pair 7 / genetics
  • Cyclin-Dependent Kinase 6 / genetics
  • Dysplastic Nevus Syndrome / enzymology
  • Dysplastic Nevus Syndrome / genetics*
  • Female
  • Founder Effect
  • Gene Deletion
  • Genes, p16*
  • Genetic Carrier Screening
  • Genetic Linkage / genetics*
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Male
  • Melanoma / enzymology
  • Melanoma / genetics*
  • Pedigree
  • Skin Neoplasms / enzymology
  • Skin Neoplasms / genetics*


  • CDK6 protein, human
  • Cyclin-Dependent Kinase 6