Transcriptional profiles of mouse melanocytes 27 days after neonatal BRAF activation and UVB radiation or LKB1 loss

BRAFV600E-induced cell growth arrest in melanocytic nevus is on debate where only one third of melanomas arise directly from nevi. We showed that simultaneous neonatal oncogene (BRAFV600E) activation and UVB irradiation prevent BRafV600E-induced growth arrest in melanocytes, allowing melanoma development. A meta-analysis of gene expression profiles of melanocytes isolated from different mouse models and numerous studies revealed multiple common genes and processes involved in preventing BRafV600E-induced growth arrest. In humans, many of these genes are associated with poor survival and are upregulated during melanoma progression and in many RAS pathway activation-driven tumors. Single-cell profiling confirmed that BRAFV600E and the identified genes cooperate in melanocyte transformation, including the acquisition of multidrug resistance features. Depletion of these genes in vitro and in vivo revealed the utility of the encoded proteins as therapeutic targets. These results support the existence of BRAFV600E-mutated melanomas unassociated with nevus progression and identify targets for melanoma treatment. There are a total of 14 samples, 11 of them were obtained from mouse melanocytes derived from Tyr::CreERT2,BRafCA mouse model, untreated (3 replicates), treated with 4-Hydroxytamoxifen (4OHT) (1µM; 48 hours) (4 replicates) and 4OHT-treated, also irradiated with UVB (30J/m2) (4 replicates). The rest of the samples (3 samples) were obtained from melanocytes derived from the Tyr::CreERT2; BRafCA/CA;Lkb1F/F mouse model, treated with 4OHT (3 replicates). Please note that different combination of samples has been used in two different analyses and the re-analyzed samples represent the common samples in both analyses.