DNA switches tied to non-Hodgkin lymphoma

Genetic defects lead to altered activity in other genes

Mutations in genes that flick other genes on and off may be at the heart of two forms of the blood cancer non-Hodgkin lymphoma.

Two separate studies found that mutations in the MLL2 gene lead to the cancer, researchers report online July 27 in Nature and July 31 in Nature Genetics. For certain subtypes of non-Hodgkin lymphoma, the mutations appear to account for most cases.

MLL2 gets put right at the top of the list,” says Ryan Morin of the British Columbia Cancer Agency in Vancouver. Morin and his colleagues found that the gene is mutated in 89 percent of cases of follicular lymphoma, a slow-growing form of the disease.

“It’s a [mutation] that defines the disease,” says Riccardo Dalla-Favera, a molecular hematologist at Columbia University and coauthor of the paper in Nature Genetics.

Both studies also found that mutations in MEF2B are associated with a form of the cancer called germinal center lymphoma.

The mutations are among 100 found in people with lymphoma, the authors of the paper in Nature Genetics estimate. This gives an idea of the landscape of genetic changes in the disease, says Dalla-Favera. “The biology is yet to be explored.”

But even with limited information about what the two newly discovered mutations do, their ubiquity in some forms of non-Hodgkin lymphoma could make them good targets for cancer-fighting drugs.

The two genes help turn other genes on and off through epigenetic changes — chemical tags on DNA or associated proteins that change the way genes operate without altering their information content. In this case, these tags influence how tightly DNA strands are wound around the spool-like proteins called histones, which package the genetic material and keep it from getting tangled up.

The researchers think the mutations interfere with gene activation in general, but that changing the activity of a small number of genes is probably what triggers the cancer.

“I don’t think epigenetics is going to have a role in every cancer, but it’s really been underappreciated,” Morin says.

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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