How do some genetic mutations affect the outcome of patients with skin melanoma?

The outcome for a type of skin cancer called melanoma can vary between different individuals. Apart from factors such as the depth of the tumour and degree of spread, the presence of markers for certain genetic changes (mutations) can also affect the disease outcome. One form of mutation ( BRAF ) is often found in younger patients with a history of intermittent exposure to too much ultraviolet light from the sun; and several targeted therapies can be effective in such patients, who have disease that has now spread to other parts of their body. On the other hand, another type of mutation ( NRAS ) is typically found in older patients with a history of chronic sun exposure; these patients respond less well to targeted therapy. Both of these mutations require an extra trigger, such as ultraviolet light, for the cells to become cancerous. In addition, frequently mutations of the promoter of the TERT gene, which are linked with damage from ultraviolet light, are associated with more aggressive tumours and a poorer outcome. In this paper, the authors from Spain and Germany looked at data from 563 patients with skin melanoma. They found that BRAF and NRAS mutations were common in the tissues they examined from these patients. The additional presence of the TERT promoter mutation worsened the outcome, particularly in patients who had the NRAS mutation. Patients without any of these mutations that they investigaged tended to have a better outcome overall. Classifying patients according to the presence or absence of these three mutations ( BRAF , NRAS and TERT ) should help in assessing disease outcome. Linked Article:  Manrique‐Silva et al . Br J Dermatol 2021; 184 :504–513.