Study Finds Mechanism That Causes Normal Cells To Become Cancerous

Researchers studying brain tumors said they have discovered a new biological mechanism that causes normal cells to become cancer cells, a finding that both challenges current treatment strategies and could lead to new approaches against the disease.

In a study published online Wednesday in the journal Nature, the researchers reported that a mutation in what are called IDH genes causes changes in how DNA is folded into the nucleus of cells. This in turn enables abnormal interactions between other genes, turning on a process that promotes the development of tumors.

“This shows us there is a whole other side of how cancer can form and progress,” said Jeremy Rich, chairman of stem cell biology and regenerative medicine at the Cleveland Clinic, who wasn’t involved with the study.

While the study focused on the brain tumor called glioma, researchers said mutant IDH genes are present in many other cancers, including leukemia, and colon and bladder cancers.

“The implications are likely to be much broader than just brain tumors,” said Bradley Bernstein, an institute member at the Broad Institute, Cambridge. Mass., and senior author of the study. He said the finding “changes our fundamental basic science view” of how disruption of the genome can cause cancer.

It also underscores cancer’s complexity. The process appears to operate independently of the so-called driver mutations that fuel cancer. The finding may help explain why treating tumors with drugs targeted at such mutations—a strategy known as precision medicine—is having limited success. While such targeted treatment often dramatically shrinks tumors initially, in most cases, patients eventually relapse.

“This puts a further dent in our ability to think that silver bullets are ready-in-the making for many cancer types,” Dr. Rich said.

Laid out end-to-end, the three billion base pairs that make up the human genome extend about 6½ feet. That has to be packaged to fit into each microscopic cell.