A Team of Researchers Unearth Crucial Gene Mutation in Critical Cancer Research
A team of researchers from the University of Chicago made a groundbreaking scientific discovery, as detailed in an article in the journal Nature on October 2, 2024. They unearthed a critical gene mutation known as TET2, which is frequently found in a host of cancers, and revealed a more comprehensive function for RNA in the regulation of human genes. Prof. Chuan He, who headed the study in partnership with Prof. Mingjiang Xu from the University of Texas Health Science Center at San Antonio, discovered that TET2 has a pivotal role in the mechanism of DNA storage and RNA modification-related packaging within cells.
Revised Perspective on the Role of RNA
The team’s groundbreaking work indicates an extensive role for RNA in the assembly of chromatin structures, a disruption of which may precipitate the onset of cancer. Prof. Chuan He, serving as both a distinguished service professor in the Department of Chemistry, the Department of Biochemistry and Molecular Biology, and as an investigator at the Howard Hughes Medical Institute, stated, “We are witnessing a conceptual shift.” He continued, emphasizing, “By presenting new therapeutic targets for different disorders, we expand the overarching framework of chromatin governance in the sphere of biology. We envision a substantial practical impact.”
The presence of TET2 mutations, found in 10–60% of human leukemia and other cancers, has long baffled researchers due to its uncertain role in disease advancement. This recent finding sheds light on how TET2 mutations perturb RNA-related operations, which play a critical role in the regulation of how genes are accessed and involved in both hematological and neurological development. Laboratory studies determined that TET2 oversees m5C methylation on RNA, modifying chromatin structures and, consequently, gene expression.
Prof. He explained, “A mutation in TET2 resurrects a channel of growth that could culminate in cancer, particularly within the blood and the brain, as these areas are where the channel seems to be most crucial.”
When examining the consequences of the study on human leukemia cells, the researchers found that thwarting the ability to generate a protein relevant to the RNA modifications led to the demise of the leukemia cells, affirming the significance of TET2’s role in cellular regulation.
New Horizons for Disease Treatment and Comprehension
This discovery heralds new prospects for therapy. Prof. He alluded to the promising strategy of engineering “a silver bullet” aimed solely at cancer cells by targeting malfunctioning pathways arising from TET2 mutations. Moreover, the insight has implications for understanding Clonal Hematopoiesis of Indeterminate Potential (CHIP), a condition prevalent in seniors that heightens the risk of various inflammatory diseases, such as heart disease and diabetes.
Prof. Caner Saygin, an oncology specialist and assistant professor of medicine at the University of Chicago Medicine, noted the absence of treatment for patients with CHIP since they don’t have cancer but expressed optimism in the potential of eliminating these mutant cells to improve patient outcomes.
Efforts are underway at the University of Chicago in collaboration with its Polsky Center for Entrepreneurship and Innovation to form a start-up that aims to harness the research findings for drug development, showcasing an intent to bridge scientific breakthroughs with real-world medical applications.
