Multiple primary melanomas in a CDKN2A mutation carrier exposed to ionizing radiation.

Abstract

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.

OBSERVATIONS:

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.

• Authors: Mark J Eliason, Chris B Hansen, Marybeth Hart, Patricia Porter-Gill, Wei Chen, Richard A Sturm, Glen Bowen, Scott R Florell, Ronald M Harris, Lisa A Cannon-Albright, Leonard Swinyer, Sancy A Leachman
• Journal: Archives of dermatology (Arch Dermatol) Vol. 143 Issue 11 Pg. 1409-12 (Nov 2007) ISSN: 1538-3652 [Electronic] United States
• PMID: 18025365 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 5' Untranslated Regions
• Receptor, Melanocortin, Type 1
• Arginine
• Cysteine

Topics

• 5' Untranslated Regions
• Adult
• Arginine
• Cysteine
• Environmental Exposure
• Female
• Genes, p16
• Genetic Predisposition to Disease
• Hair Color (genetics)
• Heterozygote
• Humans
• Melanoma (etiology, genetics, pathology)
• Mutation
• Neoplasms, Multiple Primary (etiology, genetics, pathology)
• Neoplasms, Radiation-Induced
• Nuclear Weapons
• Receptor, Melanocortin, Type 1 (genetics)
• Skin Neoplasms (etiology, genetics, pathology)