Exome_sequencing_of_zebrafish_melanoma

Melanoma is the most lethal form of skin cancer. Because of this, the primary genetic and molecular events of the disease have been well-characterized and remain an intense area of investigation. Zebrafish have shown to be a valuable model for studying melanoma. Transgenic zebrafish expressing brafV600E, an activating mutation found in >60% of human melanomas, develop ectopic melanocyte patches (moles) called fish-nevi. In the presence of a second loss-of-function mutation (e.g. in tp53, pten, mitf, or ink4a), these fish nevi can expand into invasive melanomas, but at low transformation rates (<10% of fish with nevi), thereby suggesting that additional mutations are necessary for tumourigenesis. We are interested in determining the specific genetic events underlying tumourigenesis in zebrafish models of melanoma. We are also interested in determining how these engineered initiating events affect the mutation spectrum and ultimate tumour pathology. Finally, we are interested in determining how well these events parallel those in mouse and human, an important question regarding the relevancy of zebrafish models in cancer research. To answer these questions, we will sequence the exomes of primary zebrafish melanomas generated from three engineered zebrafish models: brafV600E, mitf; brafV600E , pten; brafV600E, p53.