A NETWORK-BASED APPROACH TO INVESTIGATE THE DIFFERENT RESPONSE TO VEMURAFENIB IN BRAF V600E MUTANT CANCERS

One of the best known oncogene is the BRAF gene, implicated in cell growth, differentiation and survival processes. The most frequent mutation for the BRAF gene is the mutation BRAF V600E which appears in many tumors (melanoma, thyroid cancer, colon cancer, lung cancer, etc.) and it is often associated with a poor prognosis. The agent commonly used to treat cancer patients with BRAF V600E mutation is vemurafenib. However, numerous studies have shown that different BRAF V600E mutant cancers do not respond uniformly to the vemurafenib inhibitor. In order to investigate the reason for this phenomenon, we applied SWIM, a software able to identify putative regulatory (switch) genes involved in drastic changes to the cell phenotype, to gene expression profiles data of different BRAF V600E mutant cancers and their normal counterparts publicly available on the TCGA (The Cancer Genome Atlas). This analysis led to hypothesize that the heterogeneity in the response to vemurafenib may be due to a different number of kinases with a sequence homologous to BRAF among the switch genes of each analyzed tumor.