UV-Independent Pathway ID'd in Those at Risk for Melanoma
Thursday, November 1, 2012 (Last Updated: 11/02/2012)
THURSDAY, Nov. 1 (HealthDay News) -- Mice with an inactivating mutation in the melanocortin 1 receptor (Mc1r) gene, which controls pigment production, have a phenotype similar to red hair/fair skin in humans; these mice have an increased risk of melanoma, even in the absence of ultraviolet radiation exposure, which may act by a mechanism of oxidative damage, according to a study published online Oct. 31 in Nature.
Devarati Mitra, from the Massachusetts General Hospital in Charlestown, and colleagues used genetically engineered mice carrying an inactivating mutation in the Mc1r gene and introduced a conditional, melanocyte-targeted allele of the most common melanoma oncoprotein, BRAFV600E to investigate ultraviolet-radiation-independent carcinogenesis.
The researchers found that, without providing additional gene aberrations or ultraviolet radiation exposure, there was a high incidence of invasive melanomas in these mice. Following introduction of an albino allele to ablate all pigment production on the Mc1re/e background, selective absence of pheomelanin synthesis was found to be protective against the development of melanoma. Compared with albino-Mc1re/e mouse skin, normal-Mc1re/e mouse skin was found to have significantly greater oxidative DNA and lipid damage.
"These data suggest that the pheomelanin pigment pathway produces ultraviolet-radiation-independent carcinogenic contributions to melanomagenesis by a mechanism of oxidative damage," the authors write. "Although protection from ultraviolet radiation remains important, additional strategies may be required for optimal melanoma prevention."
Hematology & Oncology
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