New Tumor Suppressor Gene in Melanoma Discovered

melanoma

Yardena Samuels, PhD

The Weizmann Institute of Science recently revealed a new gene belonging to the tumor suppressor gene group,RASA2, which is driving a particular deadly subset of melanomas for patients with dysfunctioning RAS pathways. The understanding of this new tumor suppressor gene type has the potential to open news doors in the knowledge of the cancer’s growth and as guidance toward future treatments.¹

The study¹comes after Yardena Samuels, PhD of the Institute’s Molecular Cell Biology Department and her team searched their database of more than 500 melanoma genomes and exomes for protein-building sequences. The database explores the targeted genes crucial to understanding the cancer’s biology and is the largest to date.

“The identification of targetable alterations in melanoma is an urgent need. An in-depth understanding of the functional effects of mutations in these genes is the first step toward revealing the underlying mechanism of melanoma growth,” said Nouar Qutob, PhD, a postdoctoral fellow in Samuels’ lab and participant in the research, in a statement.

Tumor suppressor genes usually impede cell growth, especially the growth of cancer cells; however, its mutation acts as “defective brakes on cellular proliferation.”

Among the many known mutated tumor suppressor genes, the Weizmann researchers discovered a new gene that stood out in their research—theRASA2. Through examination and cloning of the normal protein and the mutated versions, the team found that theRASA2regulated a key component of the cell, the RAS.

The RAS is a part of the cell that has been known to contribute to unchecked cell growth. Upon restoring the production of protein in the cells that containedRASA2mutations, the team discovered that cells stopped growing and died.

According to the research, the mutation of theRASA2was discovered in 5.4% of human melanomas, and its expression was lost in 30% of human melanoma’s, which was found to contribute to a reduced survival rate.

Researchers indicated that patients with dysfunctional RAS pathways generally have a worse prognosis than patients with other types of melanoma. Scientists have yet to discover any treatments plans targeted specifically to the RAS 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,” said Samuels in a statement.^“We are now going to focus onRASA2, to find out what proteins it communicates with in healthy cells and melanoma, as well as in the cells’ response to targeted therapy.”

Reference

1. Weizmann Wonder Wander. A newly-discovered tumor suppressor gene affects melanoma survival. http://wis-wander.weizmann.ac.il/a-newly-discovered-tumor-suppressor-gene-affects-melanoma-survival#.VjaSXelCbFI. Accessed November 1, 2015.