Funding sources This activity was supported in part by the NIH (K24 CA149202-01 to H.T.), the American Cancer Society (RSG-07-085-01-MGO to H.T.) and the generous donors to the MGH Millennium Melanoma Fund.
CLINICAL AND LABORATORY INVESTIGATIONS
Comprehensive mutational analysis of CDKN2A and CDK4 in Greek patients with cutaneous melanoma
Article first published online: 2 NOV 2011
© 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011
British Journal of Dermatology
Volume 165, Issue 6, pages 1219–1222, December 2011
How to Cite
Nikolaou, V., Kang, X., Stratigos, A., Gogas, H., Latorre, M.C., Gabree, M., Plaka, M., Njauw, C.N., Kypreou, K., Mirmigi, I., Stefanaki, I. and Tsao, H. (2011), Comprehensive mutational analysis of CDKN2A and CDK4 in Greek patients with cutaneous melanoma. British Journal of Dermatology, 165: 1219–1222. doi: 10.1111/j.1365-2133.2011.10551.x
Conflicts of interest None declared.
The first two authors contributed equally to this study.
- Issue published online: 24 NOV 2011
- Article first published online: 2 NOV 2011
- Accepted manuscript online: 31 JUL 2011 11:30PM EST
- Accepted for publication 21 July 2011
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.