Of the hundreds of genes that can be mutated in a single case of melanoma, only a handful may be true drivers of cancer. This is a newly identified member of a group of genes called tumor suppressor genes, and is mutated in some 5.4% of melanomas. Furthermore, its expression was found to be lost in over 30% of human melanomas. Some were specifically searching for tumor suppressor genes in their database, which consists of more than 500 melanoma genomes and exomes protein-building sequences making it the largest melanoma dataset. As their name suggests, tumor suppressor genes normally inhibit cell growth, including that of cancer cells.  Indeed, the melanoma genome sequences contained mutations in known tumor suppressor genes, but there was also a new gene RASA2. Cloning of both the normal protein and the most recurrent mutated versions to see their effects on melanoma cells, finding that RASA2 regulates a key protein in the cell, called RAS.

RAS has been identified as a major oncogene that contributes to the unchecked growth of cells. When the restoration production of the RAS protein in melanoma cells are seen, then RASA2 mutations occurs, the cells stopped growing and eventually died. Patients with dysfunctional RAS pathways tend to have a worse prognosis than those with other types of melanomas. As the RAS pathway is highly dysregulated in cancer, the discovery of an alternative mechanism for its activation is likely to stimulate. Most targeted cancer therapies nowadays work by inhibiting the products of oncogenes that are overactive in melanoma cells. However, loss or mutations in tumor suppressor genes like RASA2 also contribute to melanoma development; therefore, discovering and studying RASA2 targets and partners will be our next aim.

Regards
Alice Maria
Editorial Assistant
Journal of Medical Oncology