Scientists decode key mutation in many cancers

Researchers from the University of Chicago have uncovered a critical role of RNA in regulating DNA packaging within cells, particularly involving the gene TET2. The study, published in Nature, identifies a previously unknown pathway where TET2 affects RNA, not DNA as previously thought, through a modification process called methylation. This discovery sheds light on how TET2 mutations contribute to a wide range of cancers and other disorders, especially in the blood and brain, by disrupting the packaging of chromatin, which is essential for gene expression and cellular function.

The findings explain a longstanding mystery: why TET2 mutations are so prevalent in various cancers, particularly leukemia. The research team showed that TET2 controls RNA methylation, specifically the modification known as m5C, which in turn attracts a protein called MBD6. This protein plays a key role in the chromatin packaging process, which can either facilitate or restrict access to genetic material. The study also demonstrated that disrupting this pathway by targeting MBD6 could selectively kill leukemia cells, providing a promising avenue for developing targeted cancer therapies.

Beyond cancer, the implications of TET2 mutations extend to age-related conditions like heart disease, diabetes, and other inflammatory disorders, collectively known as CHIP (clonal hematopoiesis of indeterminate potential). These mutations cause inflammatory TET2 mutant cells to circulate in the bloodstream, increasing the risk of chronic diseases. The discovery could lead to treatments that eliminate these mutant cells, potentially improving the health and lifespan of patients with CHIP. This breakthrough also suggests a broader role for RNA modifications in chromatin regulation, opening the door to further discoveries in gene expression and cellular biology.