CHAPEL HILL, N.C. Scientists around the world have been hot on the trail of a genetic mutation closely associated with some brain cancers and leukemia since the mutation's discovery in 2008. The hunt is now yielding fruit. In the Jan. 18, 2011 issue of Cancer Cell, researchers reveal how the mutation contributes to cancer development and suggest potential ways to counter its effects.
About 75 percent of people with low-grade brain tumors and 20 percent of people with acute myeloid leukemia have a mutated version of a gene known as IDH. IDH helps cells metabolize, or eat, food. "We now know that IDH represents the most frequently mutated metabolic gene in human cancer. And that changes the landscape of cancer research in metabolism quite a lot," said Yue Xiong, PhD, William R. Kenan Jr. professor of biochemistry and biophysics at the UNC Lineberger Comprehensive Cancer Center.
Xiong and collaborators at UNC, the University of California San Diego, and the Shanghai Medical College of Fudan University in China discovered that the IDH mutation sets off a battle inside cells between two metabolites, small molecules produced by metabolic enzymes. On the good sidethe side that leads to normal cell growthis a molecule called ?-KG. On the bad sidethe side that leads to canceris a molecule called 2-HG.
The researchers discovered that cells with the IDH mutation produce less ?-KG and more 2-HG than normal cells. 2-HG then outcompetes ?-KG, disabling a whole family of enzymes that depend on ?-KG to do their jobs in the cell. Normal cell functions break down, contributing to the development of cancer.
Two of the affected enzymes are also involved in controlling gene expression, so if 2-HG wins the battle, it can also activate other genes that lead to cancer growth.
Bolstering ?-KG to help fight 2-HG could offer a new treatment option for patients with the mutation. "?-KG is a natural product of the body. So we know
|Contact: Les Lang|
University of North Carolina School of Medicine