G12DNRAS and kinase-dead BRAF cooperate to drive naevogenesis and melanomagenesis


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Malin Pedersen1, Amaya Viros2, Martin Cook2, Richard Marais2
1The Institute of Cancer Research, London, UK,2The Cancer Research UK Manchester Institute, Manchester, UK

Abstract

Background

Melanoma is the most deadly form of skin cancer and is a disease that is rising in incidence. Q61 mutant NRAS and V600 mutant BRAF, the most common mutations in melanoma, are mutually exclusive unless the tumours are placed under the selective pressure of BRAF drugs, whereas some of the rare NRAS and BRAF mutants are coincident even without drug selection. Notably, where mutant RAS and BRAF are coincident, it involves codons G12 and G13 of NRAS, and codons such as G466, G469, D594 and G596 of BRAF, all of which impair or kill BRAF kinase activity.