Cancer-Related Mutation Found in DNA’s Dark Region

DNA's dark matter has yielded a cancer-related mutation that may lead to new treatments for many cancers, including chronic lymphocytic leukemia (CLL) .

What Is Junk DNA?

To describe human DNA regions outside genes, in 1972 the term Junk (insignificant, waste) DNA was first introduced. The human genome consists of %98 non-protein-coding DNA regions, and some of their mutationswere found important in a rare pediatric brain cancer, CLL, and liver cancers. U1 small nuclear RNA (U1-snRNA) mutations, mutations in U1 genes, were the subject of 2 related studies published in October 2019 in Nature .

Scientists estimate that the human genome’s dark matter contains 40.000 or more RNA genes. Although they do not encode proteins, these may regulate how and when genes are expressed in cells. The decade-long federal ENCODE (encyclopedia of DNA elements) project established that, compared with approximately % 2 of DNA encoding particular proteins, these molecules comprise approximately % 98 of our genetic blueprint.

Study Details

“We have not connected all the dots on how it causes cancer,” said Lincoln Stein, head of adaptive oncology at the Ontario Institute for Cancer Research in Toronto, Canada. He added that the team is beginning to understand the mutations' effects: disrupted normal RNA synthesis causes errors in cancer-driving genes . This genetic error, a single “typo” in DNA, occurred in more than % 90 of a rare childhood brain cancer subtype, in % 10 to % 15 of CLL cases, and in liver cancers . For this discovery, researchers analyzed approximately 2600 whole tumor genomes across 37 different cancers. “At first we found nothing new, which is quite disappointing,” said Dr. Stein. However, when his colleague Michael Taylor, a pediatric neurosurgeon and senior scientist, identified the U1 mutation in medulloblastoma tissue samples, they decided to test it in other cancers. The First Example of a Noncoding RNA with a Clear Cancer-Related Mechanism The U1 mutation also occurred in difficult-to-treat cancers with the worst prognosis, disease course. In CLL, for example, researchers identified it in more primitive, poorly differentiated lymphocytes. Similarly, liver cancer mutations occurred in cancers associated with heavy alcohol use but not hepatitis virus-related liver cancers—an unexpected finding under investigation. This discovery may also offer a new treatment opportunity : the molecular pathway causing cells with these mutations to become malignant could be targeted by new anticancer agents.