MITF may be an oncogene for familial, sporadic melanoma

Yokoyama S. Nature. 2011;doi:10.1038/nature10630.

Issue: December 10, 2011

Microphthalmia-associated transcription factor, a genetic variant that induces the production of proteins in melanocytes, appears to increase the risk for familial and sporadic malignant melanoma.

Researchers determined that microphthalmia-associated transcription factor (MITF) E318K was a medium-penetrance risk variant for melanoma. They then genotyped two large Australian melanoma case-control samples and found a carrier frequency of 0.0072 in control participants (n=1,953). From that, they concluded that MITF E318K was a rare population variant. The variant appeared in patients (n=2,059) at significantly higher carrier frequency (0.0165) compared with controls (OR=2.33; 95% CI, 1.21-4.70). Researchers said the carrier frequencies indicate that the variant correlates with increased melanoma risk in the general population.

Among patients, the MITF E318K variant was enriched in those with multiple primary melanomas (OR=4.22; 95% CI, 1.52-10.91), a family history of melanoma (OR=2.95; 95% CI, 1.23-6.92) or both (OR=8.37; 95% CI, 2.58-23.80), but not in patients whose disease appeared before the age of 40 years.

Researchers repeated their findings in a pair of population-based case-control samples from the United Kingdom. In the combined U.K. sample, the variant allele frequency was 0.0176 in patients vs. 0.0085 for controls (OR=2.09; 95% CI, 1.14-3.94). Researchers said the association between variant allele frequency and melanoma in the pooled U.K. and Australian data was highly significant (OR=2.19; 95% CI, 1.41-3.45).

Researchers next screened for the variant in 182 families from the United Kingdom and 88 families from Australia with more than one diagnosis of melanoma. E318K was more common in families with three cases (7.4%) compared with those with two cases (0.8%).

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