title: Comprehensive mutational analysis of CDKN2A and CDK4 in Greek patients with cutaneous melanoma.
abstract: BACKGROUND
  The penetrance of CDKN2A mutations is subject to geographical and latitudinal variation and is presumably dictated by ultraviolet radiation exposure and possibly other co-inherited genetic factors. The frequency of mutations increases with the number of family members affected and the number of primary tumours, and also fluctuates with geography. To date, little is known about the prevalence of CDKN2A mutations in patients with melanoma from Greece.
  
  
  OBJECTIVE
  To characterize the frequency of CDKN2A and CDK4 mutations in a hospital-based population of Greek patients with melanoma.
  
  
  METHODS
  Three hundred and four consecutive single primary melanoma (SPM), nine familial melanoma (FM) and seven multiple primary melanoma cases (MPM) were assessed for sequence variants in exons 1α, 1β and 2 of CDKN2A and exon 2 of CDK4.
  
  
  RESULTS
  Germline CDKN2A mutations were detected in 10 of 304 SPM (3·3%), in four of seven MPM (57%) and in two of nine FM (22%) cases. The most common mutation was a Northern European allele (p16 p.R24P) detected in eight individuals. Five previously unreported CDKN2A variants were also identified: -34G>C, c.41_43delins20bp, c.301G>C (p.G101R), c.301G>A (p.G101E) and c.296_297insGACC. We also describe the first report of a CDK4 p.R24H substitution in a Greek family.
  
  
  CONCLUSIONS
  The Greek population appears to harbour a higher prevalence of the CDKN2A mutation than other reported cohorts. This supports the notion that genetic susceptibility may play a stronger influence in a country with a relatively low incidence of melanoma. Furthermore, the identification of Northern European alleles suggests that gene migration may be responsible, in part, for the observed cases in Greece.
authors.affiliation: Department of Dermatology, University of Athens Medical School, 'A. Sygros' Hospital, I Dragoumi 5, 16121 Athens, Greece.
authors.forename: V
authors.initials: V
authors.lastname: Nikolaou
authors.forename: X
authors.initials: X
authors.lastname: Kang
authors.forename: A
authors.initials: A
authors.lastname: Stratigos
authors.forename: H
authors.initials: H
authors.lastname: Gogas
authors.forename: M C
authors.initials: MC
authors.lastname: Latorre
authors.forename: M
authors.initials: M
authors.lastname: Gabree
authors.forename: M
authors.initials: M
authors.lastname: Plaka
authors.forename: C N
authors.initials: CN
authors.lastname: Njauw
authors.forename: K
authors.initials: K
authors.lastname: Kypreou
authors.forename: I
authors.initials: I
authors.lastname: Mirmigi
authors.forename: I
authors.initials: I
authors.lastname: Stefanaki
authors.forename: H
authors.initials: H
authors.lastname: Tsao
mesh_terms: D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D019942:Genes, p16 / Q000502:physiology*; D018095:Germ-Line Mutation / Q000235:genetics*; D006115:Greece; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D021141:Nucleic Acid Amplification Techniques; D010375:Pedigree; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: D051358:Cyclin-Dependent Kinase 4