Sunday, April 14, 2024

Common gene mutation increases cancer risk, research indicates

Researchers at the University of Virginia School of Medicine have discovered how a common gene mutation robs people of natural cancer protection. Hao Jiang of the UVA Cancer Center and his collaborators have revealed why a mutation in the UTX gene disrupts cells’ ability to suppress tumors. The gene product, they found, forms tiny droplets in cells that help prevent tumour formation. But the mutation throws a wrench in that important process, leaving affected people vulnerable. The new understanding of this vulnerability will help scientists and doctors as they seek better ways to battle and prevent cancer. “How UTX inactivation causes human cancers remained elusive, as we did not know its key molecular activity that is critical for tumour suppression, posing a barrier to cancer therapies targeting UTX-related pathways,” said Jiang. “Our work largely solved this mystery. Moreover, it suggests that disruption or alterations of these droplets can profoundly affect how our cells fight cancer. Forming proper droplets is likely to be a fundamental mechanism that maintains cellular health, and we are just beginning to understand.” Jiang’s work presents a fascinating glimpse into an important way our bodies keep us safe from cancer. The UTX gene, he found, plays a vital role by directing the formation of “condensates” inside cells to prevent tumour formation. These little droplets condense from material in cells, and once the droplets have formed, important biological processes can take place. The droplets are important not just for suppressing tumors, Jiang and his team found, but for directing embryonic stem cells, generalized cells that can turn into highly specialized cells. For example, a stem cell might turn into a nerve cell or become bone. For tumour suppression, the researchers found, the droplets control the activity of chromatin, the genetic material contained in our chromosomes. This ensures chromatin’s “optimal activity,” the scientists write in a new paper in Nature. The interaction, they note, “ensures efficient and correct chromatin modifications and interactions to orchestrate a proper tumour-suppressive transcriptional program.” Mutation of the UTX gene, however, robs cells of this important ability, putting people with the mutation at risk for cancer, the researchers concluded.

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