Genes make potential target in lymph cancer
By Nathan Seppa
Treatment of the lymph node cancer called diffuse large B-cell lymphoma is all-or-nothing. Chemotherapy cures about 40 percent of patients, but the others eventually die from this cancer. Because of that split, scientists deduce that the cancer cells–although outwardly similar–must vary from patient to patient.
The lymphoma arises in immune cells that reside in lymph nodes, and it causes tumors there. In the January Nature Medicine, researchers report that a gene called NOR1 is highly active in the diffuse large B-cell lymphoma tumors of people for whom chemotherapy has succeeded. But this gene is less active in patients for whom the drugs failed. NOR1 encodes a protein that plays a role in the normal self-destruction, or apoptosis, of damaged cells.
Hypothetically, excess NOR1 protein could help limit cancer, particularly because much of chemotherapy is designed to induce apoptosis in malignant cells, says study coauthor Margaret A. Shipp, a molecular biologist at the Dana-Farber Cancer Institute and Harvard Medical School in Boston.
Two other genes–dubbed PDE4B and PKC-beta–are more active in patients in whom the lymphoma is ultimately fatal than in the other group, the researchers report. PDE4B and PKC-beta encode enzymes that seem to enhance cell growth. Although their precise roles are poorly understood, the enzymes may waylay inhibitors of cell growth, says Shipp.
She and her colleagues used a technique called microarray analysis, in which they spread DNA from lymphoma cells on microchips that reveal gene
activity.
To assess differences between patient groups, the scientists analyzed activity of 6,817 genes. They examined tissue samples from 58 people with the lymphoma. Some had been cured by chemotherapy, while others had died despite it.
The researchers eliminated genes that were uniformly active or quiet in both groups, Shipp says. Then, the team zeroed in on genes that earlier research had suggested were active in this lymphoma and might play a role in either hindering or abetting cell growth. The microarray analysis revealed significant differences in activity of NOR1, PDE4B, and PKC-beta between the two patient groups.
“A cancer might be more responsive to chemotherapy [when] it lacks genes that prevent cell death,” says Louis M. Staudt, a molecular biologist at the National Cancer Institute in Bethesda, Md. However, he says, microarray analysis has its limits. “Just seeing a gene [active] in a cell doesn’t make it a target” for direct therapy, he says. Scientists must first determine the biological role of the protein encoded by the gene to ascertain whether it’s a pivotal player in the cancer, he says.
Shipp agrees. She and her colleagues are now studying other genes highlighted by their analyses. The work, she says, might eventually reveal which patients would benefit from chemotherapy or even lead to new treatments that would bolster or inhibit specific genes and thus offer an alternative to chemotherapy.
