Melanoma prone families with CDK4 germline mutation: phenotypic profile and associations with MC1R variants
Year: 2013
Type: article
Study design: Observational Study
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.
Source: Journal of Medical Genetics
Authors: Hanne Eknes Puntervoll, Xiaohong R Yang, Hildegunn Høberg Vetti, Ingeborg M Bachmann, Marie Françoise Avril, Meriem Benfodda, Caterina Catricalà, Stéphane Dalle, Anne B Duval-Modeste, Paola Ghiorzo, Paola Grammatico, Mark Harland, Nicholas K Hayward, Hui-Han Hu, Thomas Jouary, Tanguy Martin-Denavit, Aija Ozola, Jane M Palmer, Lorenza Pastorino, Dace Pjanova, Nadem Soufir, Solrun J Steine, Alexander J Stratigos, Luc Thomas, Julie Tinat, Hensin Tsao, Rūta Veinalde, Margaret A Tucker, Brigitte Bressac-de Paillerets, Julia A Newton-Bishop, Alisa M Goldstein, Lars A Akslen, Anders Molven
Institutions: University of Bergen, National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Haukeland University Hospital, Hôpital Cochin, Assistance Publique – Hôpitaux de Paris, Université Paris Descartes, Inserm, Hôpital Saint-Louis, HIPI - Immunologie humaine, physiopathologie et immunithérapie, San Gallicano Hospital, Lyon 1 Université, Hospices Civils de Lyon, Hôpital Lyon Sud, Centre Hospitalier Universitaire de Rouen, Ospedale Policlinico San Martino, University of Genoa, Azienda Ospedaliera San Camillo-Forlanini, Sapienza University of Rome, St James's University Hospital, QIMR Berghofer Medical Research Institute, Latvian Biomedical Research and Study Centre, National and Kapodistrian University of Athens, Andreas Sygros Hospital, Massachusetts General Hospital, Institut Gustave Roussy
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: Cancer Research UK, European Commission, Institut National de la Santé et de la Recherche Médicale, Ministero della Salute, Ligue Contre le Cancer, Sapienza Università di Roma, Universitetet i Bergen, Latvijas Zinātnes Padome, Institut National Du Cancer, Hospices Civils de Lyon, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, National Cancer Institute
OpenAlex ID: W2168219489