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Cutaneous Melanoma Study

What is melanoma?

Melanoma is a cancer in a type of skin cells called melanocytes. Melanocyes are the cells that produce melanin, which colors the skin. When exposed to sun, these cells make more melanin, causing the skin to darken or tan. Melanoma can occur anywhere on the body and risk factors include fair complexion, family history of melanoma, and being exposed to natural or artificial sunlight over long periods of time. Melanoma is most often discovered because it has metastasized, or spread, to another organ, such as the lymph nodes. In many cases, the primary skin melanoma site is never found. Because of this challenge, TCGA is studying primarily metastatic cases (in contrast to other cancers selected for study, where metastatic cases are excluded). For 2011, it was estimated that there were 70,230 new cases of melanoma and 8,790 deaths from the disease1. Additional information on melanoma.

What have TCGA researchers learned about melanoma?

  • Four major subtypes of cutaneous melanoma were established: BRAF mutant, RAS mutant, NF1 mutant, and Triple Wild-Type.
  • Mutations in each of the identified driver genes, BRAF, RAS, and NF1, contribute to deregulation of the MAPK/ERK pathway, leading to uncontrolled cell growth.
  • The most common subtype found was the BRAF subtype, with 52% of tumors harboring BRAF somatic mutations.
  • Distinct molecular profiles of cutaneous melanoma may help clinicians improve diagnosis and treatment
    • Tumors of Triple Wild-Type patients often contained mutations in receptor tyrosine kinases that may be responsive to receptor tyrosine kinase inhibitors
    • RAS and NF1 mutant melanomas have deregulated MEK signaling, indicating that these subtypes may be responsive to MEK inhibitors
    • RAS, NF1, and Triple Wild-Type cancers all demonstrated overexpression of AKT3, a protein kinase that affects MEK and mTOR signaling pathways, suggesting that MEK and PI3K/AKT/mTOR pathway inhibitors could target this molecular alteration
  • The immune system plays a role in cutaneous melanoma:
    • Patients with metastatic melanoma with greater numbers of immune cells infiltrating tumors in the lymph nodes and enhanced T-cell signaling experienced better outcomes
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