Melanoma and neurofibromatosis: genetic diseases linked by dark skinned mouse mutants

Melanoma is the most dangerous type of skin cancer. The incidence and rate of death from melanoma is rising in Canada. Since 1988, the death rate from melanoma increased 41% in men and 23% in women, which is the highest rate of increase for any type of cancer. Melanoma is primarily caused by repeated sun damage, which leads to the accumulation of mutations in the genes that regulate the survival and growth of pigment cells in the skin. The disease has a molecular basis, so it only makes sense that a molecular approach is being taken to find new therapies to treat this deadly disease. Dr. Catherine Van Raamsdonk is taking a unique molecular approach to identify genes that may be involved in melanoma. By studying three mouse strains that have a darker dermis (the lower-most layer of the skin), Dr. Van Raamsdonk and her colleagues have discovered three genes named GNAQ, GNA11 and NF1 that are important for pigment cell growth and survival. By studying how these genes interact with each other and how they are regulated at different stages of development, she hopes to understand how they may contribute to melanoma. This work will help to reveal the molecular basis of melanoma as well as other cancers. For example, the NF1 gene is also mutated in human neurofibromatosis, a genetic disease in which patients develop disfiguring tumors and hyper-pigmentation of the skin. Dr. Van Raamsdonk and her colleagues have also discovered that GNAQ and GNA11 are mutated in 78% of human uveal melanomas, the most common type of eye cancer. This breakthrough is significant because the mutations associated with uveal melanoma were previously unknown. Dr. Van Raamsdonk is the only professor in the world examining the role of GNAQ and GNA11 in mouse pigment cells, making this work unique and essential. The information she gains may be used to prevent, diagnose, and treat different types of cancers, including melanomas.