Multiple primary melanomas in a CDKN2A mutation carrier exposed to ionizing radiation.
BACKGROUND
Recent research has shown a possible causal relationship between ionizing radiation exposure and melanoma. Individuals with mutations in CDKN2A (cyclin-dependent kinase inhibitor 2A), the major melanoma predisposition gene, have an increased susceptibility to melanoma-promoting exposures, such as UV light. We describe a patient from a familial melanoma pedigree with 7 primary melanomas on the right side of her body, the first occurring 5 years after exposure to atmospheric nuclear bomb testing in the 1950s.


METHODS
Physical examination revealed phototype I skin, red hair, and 26 nevi (14 on the right and 12 on the left side of her body). One nevus was larger than 5 mm, and 2 were clinically atypical. Sequence analysis demonstrated a known deleterious mutation in CDKN2A (G-34T) and homozygosity for a red hair color variant in MC1R (melanocortin 1 receptor) (R151C). Fluorescence in situ hybridization analysis of blood, fibroblasts, and melanocytes from both upper extremities ruled out mosaicism.


CONCLUSIONS
Individuals such as this patient, who has CDKN2A and MC1R mutations, are likely to be more susceptible to environmental insults. A careful review of environmental exposures in these vulnerable cases may reveal cancer-promoting agents, such as ionizing radiation, that go unnoticed in less susceptible populations.
Eliason
Mark J
MJ
Department of Dermatology, Health Sciences Center, University of Utah, Salt Lake City, UT 84112-5550, USA.
Hansen
Chris B
CB
Hart
Marybeth
M
Porter-Gill
Patricia
P
Chen
Wei
W
Sturm
Richard A
RA
Bowen
Glen
G
Florell
Scott R
SR
Harris
Ronald M
RM
Cannon-Albright
Lisa A
LA
Swinyer
Leonard
L
Leachman
Sancy A
SA
D020121:5' Untranslated Regions; D000328:Adult; D001120:Arginine; D003545:Cysteine; D004781:Environmental Exposure; D005260:Female; D019942:Genes, p16; D020022:Genetic Predisposition to Disease; D006200:Hair Color / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008545:Melanoma / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D009381:Neoplasms, Radiation-Induced; D054043:Nuclear Weapons; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D012878:Skin Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology
D020121:5' Untranslated Regions; D044102:Receptor, Melanocortin, Type 1; D001120:Arginine; D003545:Cysteine