TY - JOUR
TI - Melanoma prone families with CDK4 germline mutation: phenotypic profile
and associations with MC1R variants
AU - Puntervoll, Hanne Eknes
AU - Yang, Xiaohong R.
AU - Vetti, Hildegunn
AU - Hoberg
AU - Bachmann, Ingeborg M.
AU - Avril, Marie Francoise and
AU - Benfodda, Meriem
AU - Catricala, Caterina
AU - Dalle, Stephane and
AU - Duval-Modeste, Anne B.
AU - Ghiorzo, Paola
AU - Grammatico, Paola and
AU - Harland, Mark
AU - Hayward, Nicholas K.
AU - Hu, Hui-Han
AU - Jouary,
AU - Thomas
AU - Martin-Denavit, Tanguy
AU - Ozola, Aija
AU - Palmer, Jane M.
AU - and Pastorino, Lorenza
AU - Pjanova, Dace
AU - Soufir, Nadem
AU - Steine,
AU - Solrun J.
AU - Stratigos, Alexander J.
AU - Thomas, Luc
AU - Tinat, Julie
AU - and Tsao, Hensin
AU - Veinalde, Ruta
AU - Tucker, Margaret A. and
AU - Bressac-de Paillerets, Brigitte
AU - Newton-Bishop, Julia A. and
AU - Goldstein, Alisa M.
AU - Akslen, Lars A.
AU - Molven, Anders
JO - JOURNAL OF MEDICAL GENETICS
PY - 2013
VL - 50
TODO - 4
SP - 264-U82
PB - BMJ Publishing Group
SN - 0022-2593
TODO - 10.1136/jmedgenet-2012-101455
TODO - null
TODO - 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.
ER -