Jump to content Jump to navigation
Register for free e-alerts

last updated April 2013

HIGHLIGHTS

Unmasking a marker of melanoma

2 May 2012

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.

Reference

1. Yokoyama, S.,1,13 Woods, S.L.,2,13 Boyle, G.M.,2,13 Aoude, L.G.,2,13 MacGregor, S.,2,13 Zismann, V.,3,13 Gartside, M.,2 Cust, A.E.,4 Haq, R.,1 Harland, M.,5 Taylor, J.C.,5 Duffy, D.L.,2 Holohan, K.,2 Dutton-Regester, K.,2 Palmer, J.M.2 et al., A novel recurrent mutation in MITF predisposes to familial and sporadic melanoma. Nature 480, 99–103 (2011).| article |

Authors and Affiliations

  1. Department of Dermatology, Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Massachusetts 02114, USA
  2. Queensland Institute of Medical Research, Brisbane, Queensland 4029, Australia
  3. Translational Genomics Research Institute, Phoenix, Arizona 85004, USA
  4. Cancer Epidemiology and Services Research, Sydney School of Public Health, Sydney Medical School, The University of Sydney, New South Wales 2006, Australia
  5. Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, Cancer Research UK Clinical Centre at Leeds, St James’s University Hospital, Leeds LS9 7TF, UK
  6. Westmead Institute of Cancer Research, University of Sydney at Westmead Millennium Institute and Melanoma Institute Australia, Westmead, New South Wales 2145, Australia
  7. Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, School of Population Health, University of Melbourne, Victoria 3052, Australia
  8. Viertel Centre for Research in Cancer Control, The Cancer Council Queensland, Brisbane, Queensland 4004, Australia
  9. Cancer Epidemiology Centre, The Cancer Council Victoria, Carlton, Victoria 3053, Australia
  10. University of Cambridge, Cambridge CB1 8RN, England, UK
  11. Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Massachusetts 02114, USA
  12. Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Gaithersburg, Maryland 20892, USA
  13. These authors contributed equally to this work.