In a study of 501 genomes and protein-building sequences, called exomes, researchers found a newly identified member of a group of tumor suppressor genes is mutated in about 5.4% of melanomas. And these melanomas make up a particularly deadly subset in the skin cancer. Learn more
In a study of 501 genomes and protein-building sequences, called exomes, researchers found a newly identified member of a group of tumor suppressor genes is mutated in about 5.4% of melanomas. And these melanomas make up a particularly deadly subset in the skin cancer.
Israeli, Australian and U.S. researchers collaborated on this work, which reveals that recurrent loss of function mutations in a newly discovered gene, RASA2, was associated with increased RAS activation, melanoma cell growth and migration. RASA2 expression was lost in 30% or more of human melanomas and was linked to reduced survival, according to the study.
The finding marks a different approach for targeted cancer therapies, which are focused on inhibiting oncogenic overactivity in melanoma cells. This study looks at how loss or mutations in tumor suppressor genes, such as RASA2, might also contribute to melanoma development and, ultimately, could be a target for cancer therapies.
Study author Yardena Samuels, M.Sc., Ph.D., associate professor of molecular cell biology at The Weizmann Institute of Science in Israel, and her team were studying tumor suppressor genes in the Weizmann Institute’s database of melanoma genomes and exomes, which is the largest melanoma dataset available today. While tumor suppressor genes are known to inhibit cancer and other cell growth, mutated tumor suppressor genes “act like defective brakes on cellular proliferation,” according to a press release on the study.
These researchers, like others, found that melanoma genome sequences contained mutations in known tumor suppressor genes. What stood out in this study, however, was the potential impact of RASA2 mutation.
To better understand the gene’s role, Dr. Samuels and colleagues cloned the normal protein and the most recurrent mutated versions to determine their effects on melanoma cells. They found RASA2 regulates the key cell protein RAS, which researchers have identified as a major oncogene contributing to unchecked cell growth. When the researchers restored RAS protein production in melanoma cells with RASA2 mutations, the cells stopped growing and eventually died.
These findings identify RASA2 inactivation as a melanoma driver, according to the study.
“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,” Dr. Samuels said in the release.