last updated April 2013
Unmasking a marker of melanoma
Whole-genome sequencing reveals a mutation that predisposes carriers to melanoma
The risk of contracting melanoma, the largest single cause of death from skin cancer, is influenced by both environmental and genetic factors. Whereas exposure to ultraviolet radiation poses the greatest environmental risk, genetic predisposition to melanoma is more complex. Most evidence points to mutations in the CDKN2A and CDK4 genes, although these do not account for most cases.
Now, a large consortium of geneticists, led by Kevin Brown from the USA’s National Institutes of Health, has revealed an additional culprit1: a mutation in the gene encoding microphthalmia-associated transcription factor (MITF), which blocks a reversible modification of the MITF protein with a tag called SUMO. The mutation causes misregulation of several MITF-regulated genes associated with pigment-producing cells known as melanocytes.
Analysis of populations from Australia and the United Kingdom showed that the variant copy of the MITF gene was frequently associated with increased numbers of naevi (moles) and non-blue eye color, but not with other features commonly linked to a predisposition to melanoma, including blonde or red hair, fair skin, or freckling.
The findings underscore the importance of regulated protein modification in preventing disease. Individuals carrying the mutation might prolong their lives by minimizing excessive sun exposure and avoiding tanning beds.