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Newly Discovered Tumor-Suppressor Gene Affects Melanoma Survival

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Key Points

  • RASA2 is a newly identified tumor-suppressor gene that is mutated in some 5.4% of melanomas.
  • Its expression was found to be lost in over 30% of human melanomas; this loss, according to the research, was associated with reduced patient survival.
  • RASA2 regulates the key protein RAS. When the team restored the production of the RAS protein in melanoma cells that harbored RASA2 mutations, the cells stopped growing and eventually died.

Of the hundreds of genes that can be mutated in a single case of melanoma, only a handful may be true drivers of cancer. A new study published by Arafeh et al in Nature Genetics, a Weizmann Institute of Science team has revealed one of the drivers of a particularly deadly subset of melanomas that is seeing a rise in new cases. This driver, a tumor-suppressor gene called RASA2, is mutated in some 5.4% of melanomas.

Furthermore, the expression of RASA2 was found to be lost in over 30% of human melanomas; this loss, according to the research, was associated with reduced patient survival. The discovery might open new doors to understanding how this cancer grows and spreads and may lead to new directions in treatment.

Largest Melanoma Dataset

Yardena Samuels, PhD, and her team in the Weizmann Institute of Science’s Department of Molecular Cell Biology were specifically searching for tumor-suppressor genes in their database, which consists of more than 500 melanoma genomes and exomes, making it the largest melanoma dataset to date. 

The melanoma genome sequences contained mutations in known tumor-suppressor genes, but RASA2 stood out during the team’s search. They cloned both the normal protein and the most recurrent mutated versions to see their effects on melanoma cells, finding that RASA2 regulates RAS, a key protein in the cell. When the team restored the production of the RAS protein in melanoma cells that harbored RASA2 mutations, 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, and until now, scientists have not managed to create drugs that can target this pathway. “As the RAS pathway is highly dysregulated in cancer, the discovery of an alternative mechanism for its activation is likely to stimulate an avalanche of further research in this field, and is highly likely to have direct clinical relevance. We are now going to focus on RASA2, to find out what proteins it communicates with in healthy cells and melanoma, as well as in the cells’ response to targeted therapy,” said Dr. Samuels.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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