Abstract for presentation at 11th International Congress of Human Genetics

The multiple faces of melanoma: genotype-phenotype relationships and their impact on health care

  • Daniel Pinkel, University of California San Francisco, United States
  • Dr John Curtin, University of California San Francisco, United States
  • Dr Jurgen Bauer, University of California San Francisco, United States
  • Dr Jane Fridlyand, University of California San Francisco, United States
  • Dr Amaya Viros, University of California San Francisco, United States
  • Dr Phillip LeBoit, University of California San Francisco, United States
  • Dr Boris Bastian, University of California San Francisco, United States

    • Cutaneous melanoma is diverse in its presentation and etiology, but is relatively uniform in its relentless progression once invasion begins. While sun exposure is clearly a causal factor in light skinned individuals, tumors can occur on skin that has very low to no exposure in all populations. Progress in understanding and treating melanoma requires determining whether this heterogeneity represents a continuum of one entity, or a range of subtypes. Investigation of formalin fixed primary tumors using CGH, targeted gene sequencing, and expression analysis has found four subtypes, distinguishable based on their genetic aberrations and relationship to sun exposure. Acral and mucosal melanomas occur on skin with little or no sun exposure and their genomes contain frequent amplifications. However, the regions that are amplified differ significantly. Tumors occurring on sun exposed skin have much lower frequencies of amplifications, but their genomes also differ from each other depending whether or not there has been sufficient exposure to produce chronic sun damage. Moreover,mutations in BRAF occur in ~ 60% of tumors on skin that has been subject to intermittent sun exposure, but are infrequent in tumors on skin with chronic sun damage (high exposure) and on acral and mucosal sites (low sun exposure). Benign melanocytic tumors also show genetic distinctions. Nevi occurring on sun-exposed skin have very high frequencies of mutations in BRAF, while true congenital nevi, which develop in utero, have NRAS mutations and no mutations in BRAF. This complexity suggests that there is a mix of etiologic factors and inherited susceptibilities that affect many aspects melanoma development, including which benign lesions are at risk to progress. Understanding the genetic basis of individual tumors is critical for evaluating novel therapeutic options in this highly lethal disease, so that effectiveness if a specific subset of tumors is not missed.

    Conference Organiser - ICMS Pty Ltd