Poster presentation, P128

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Genetic variation in zebrafish melanoma

Melanoma is the most lethal form of skin cancer and with its incidence rising rapidly it is important to determine the role of genetic components of this disease and develop specific and effective therapeutics. The recent discovery of recurrent mutations in the melanoma genome has provided greater understanding of how melanomas develop and progress, as well as giving an opportunity for the development of new targeted drugs. The most common mutation identified in melanoma is in the BRAF proto-oncogene, which is found in 50-60% of malignant melanomas. Targeted therapies including specific BRAF inhibitors have been developed in light of this discovery, but as yet there is no effective single-agent drug to treat metastatic melanoma. It is known that other mutations, such as p53 and PTEN, co-operate with BRAF mutations in progression of melanoma from the initial benign nevus stage. If future therapies are to be effective, drug development must take these co-operating mutations into account to improve current treatment of melanoma patients. Our group has generated a model of melanoma in zebrafish that is based on the most frequently mutated gene in melanoma, BRAF. We are using this model to identify new melanoma genes and investigate the role of these genes in melanoma initiation and progression. The aim of my project is to identify the genetic differences between zebrafish melanomas with varying driver mutations; BRAFV600E with p53, PTEN or MITF. I am carrying out both exome and transcriptome sequencing of these melanomas in the hope that it will provide a novel insight into the genetics of melanoma formation and may identify new genes that affect melanoma progression.

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