The presence of well-defined intermediate stages of cancer development will provide the blueprint for marker/signature analysis of transcriptome, epigenome and proteome. Even more ideal would be a flexible model suitable for genetic manipulation, in vivo imaging and pharmacogenomic approaches. Our model is amenable to all these approaches and in the following paragraphs we will GW-572016 briefly discuss the main findings obtained with this versatile melanoma model. One of the features of our model is the development of a hyper-pigmentation phenotype at early larval stages which is suitable for large scale chemical screens aimed at discovering drugs that controls melanocyte number, migration and transformation. One important question here is whether larval hyperpigmentation in our model is associated with melanoma development. From these data it appears that c-kit signaling controls proliferation, size and migration of melanoblasts and melanocytes. However an increase of kit signaling is not per se able to induce transformation of these cells and to sustain melanoma development. Conversely, congenital nevi in children frequently harbor RAS, but not BRAF Oligomycin A purchase mutations and are associated with an increasing risk of melanoma development. In our model the expression of oncogenic ras in larval melanocytes or their precursors is able to induce them to proliferate, subvert their interactions with neighbouring cells promoting multilayer growth, causes changes in shape and migration, induces polyploidy and alter their normal development. Both somatic and germline expression of HRASV12 in kita+ cells can induce melanoma development from larval stages. This observation suggests that there is a continuum between transformed larval melanocytes and various grades of melanocytic lesions up to melanoma, which makes the larval hyperpigmentation phenotype a truly pre-melanoma phenotype. The parallels between congenital RAS-induced nevi and the clusters of transformed melanocytes in transgenic larvae suggest that the kita-GFP-RAS line could be a useful model for this condition. One of the most debated concepts in cancer research is the ability of oncogenes to transform. Decades of studies have revealed that not all cells respond to oncogenes by generating cancer. Very efficient tumor suppressor mechanisms exist that control the cell response to oncogenes, making them harmless, and these include apoptosis and cellular senescence. This is why most tumors develop only following two causative hits: firstly a mutation that transform a cellular gene in an oncogene, and secondly, a mutation that inactivate a tumor suppressor.