This year the team has just published a really important paper looking at people who hadn’t had a gene identified in their skin – in other words, they didn’t have either the NRAS spelling mistake gene changes or the BRAF spelling mistake gene change. In this group of patients, we looked for something called gene fusions, previously found in some patients with CMN by other research teams, which is where there are no spelling mistakes but two genes get stuck together, which they shouldn’t be.  This phenomenon stops the gene from doing its normal function causing the skin problems associated with CMN. We found these fusions in about half of the patients who didn’t previously have a known gene, and most of the fusions we found were with the same gene BRAF.  We also found that the fusions were probably responsible for making the CMN very itchy and very prone to growing firm lumps/ridges. Through the biopsies collected from patients participating in our research study, we were able to extract the skin cells containing the fusions and conduct a detailed analysis of their effects. Our study found that the skin cells containing BRAF gene fusions grew much faster than cells containing NRAS/BRAF spelling mistakes or no mistakes at all. This could explain why some patients develop lumps, as the cells with the fusions divide excessively. We used these cells to test the effectiveness of Trametinib, a medicine known to regulate cell division, as a potential treatment. In the lab we found that treating the cells with Trametinib reduced their excessive division, returning them to a more normal behaviour, which prompted us to use it to treat three patients (two of whom were published). The treatment has been effective in reducing lumps and itch and has been really helpful to the patients and their families.

Sara Barberan, Postdoctoral Researcher in Professor Veronica Kinsler’s lab
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