Melanoma prone families with CDK4 germline mutation: phenotypic profile and associations with MC1R variants

作者：Puntervoll Hanne Eknes; Yang Xiaohong R; Vetti Hildegunn Hoberg; Bachmann Ingeborg M; Avril Marie Francoise; Benfodda Meriem; Catricala Caterina; Dalle Stephane; Duval Modeste Anne B; Ghiorzo Paola; Grammatico Paola; Harland Mark; Hayward Nicholas K; Hu Hui Han; Jouary Thomas; Martin Denavit Tanguy; Ozola Aija; Palmer Jane M; Pastorino Lorenza; Pjanova Dace; Soufir Nadem; Steine Solrun J; Stratigos Alexander J; Thomas Luc; Tinat Julie; Tsao Hensin

来源：Journal of Medical Genetics, 2013, 50(4): 264-U82.

DOI：10.1136/jmedgenet-2012-101455

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. %26lt;br%26gt;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. %26lt;br%26gt;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%26lt;0.001). MPM subjects had a higher frequency of MC1R red hair colour variants compared with subjects with one tumour (p=0.010). %26lt;br%26gt;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.

• 出版日期2013-4
• 单位河北医科大学