@article{3157064,
    title = "Melanoma prone families with CDK4 germline mutation: phenotypic profile
and associations with MC1R variants",
    author = "Puntervoll, Hanne Eknes and Yang, Xiaohong R. and Vetti, Hildegunn and Hoberg and Bachmann, Ingeborg M. and Avril, Marie Francoise and and Benfodda, Meriem and Catricala, Caterina and Dalle, Stephane and and Duval-Modeste, Anne B. and Ghiorzo, Paola and Grammatico, Paola and and Harland, Mark and Hayward, Nicholas K. and Hu, Hui-Han and Jouary, and Thomas and Martin-Denavit, Tanguy and Ozola, Aija and Palmer, Jane M. and and Pastorino, Lorenza and Pjanova, Dace and Soufir, Nadem and Steine, and Solrun J. and Stratigos, Alexander J. and Thomas, Luc and Tinat, Julie and and Tsao, Hensin and Veinalde, Ruta and Tucker, Margaret A. and and Bressac-de Paillerets, Brigitte and Newton-Bishop, Julia A. and and Goldstein, Alisa M. and Akslen, Lars A. and Molven, Anders",
    journal = "JOURNAL OF MEDICAL GENETICS",
    year = "2013",
    volume = "50",
    number = "4",
    pages = "264-U82",
    publisher = "BMJ Publishing Group",
    issn = "0022-2593",
    doi = "10.1136/jmedgenet-2012-101455",
    abstract = "Background CDKN2A and CDK4 are high risk susceptibility genes for
cutaneous malignant melanoma. Melanoma families with CDKN2A germline
mutations have been extensively characterised, whereas CDK4 families are
rare and lack a systematic investigation of their phenotype.
Methods All known families with CDK4 germline mutations (n=17) were
recruited for the study by contacting the authors of published papers or
by requests via the Melanoma Genetics Consortium (GenoMEL). Phenotypic
data related to primary melanoma and pigmentation characteristics were
collected. The CDK4 exon 2 and the complete coding region of the MC1R
gene were sequenced.
Results Eleven families carried the CDK4 R24H mutation whereas six
families had the R24C mutation. The total number of subjects with
verified melanoma was 103, with a median age at first melanoma diagnosis
of 39 years. Forty-three (41.7%) subjects had developed multiple
primary melanomas (MPM). A CDK4 mutation was found in 89 (including 62
melanoma cases) of 209 tested subjects. CDK4 positive family members
(both melanoma cases and unaffected subjects) were more likely to have
clinically atypical nevi than CDK4 negative family members (p<0.001).
MPM subjects had a higher frequency of MC1R red hair colour variants
compared with subjects with one tumour (p=0.010).
Conclusion Our study shows that families with CDK4 germline mutations
cannot be distinguished phenotypically from CDKN2A melanoma families,
which are characterised by early onset of disease, increased occurrence
of clinically atypical nevi, and development of MPM. In a clinical
setting, the CDK4 gene should therefore always be examined when a
melanoma family tests negative for CDKN2A mutation."
}