Gene Chip Predicts Outcome of Cancer Therapy

Because cancer patients with the same diagnosis often vary widely in their response to treatment, researchers have long suspected that they might be dealing with different types of tumors. Now a team has confirmed that hunch: A DNA-studded chip has shown that one type of lymph system cancer can begin in two different parts of the immune system. Using that information, the investigators could predict which patients were most likely to benefit from chemotherapy. The work paves the way toward blending drug cocktails to fit a patient's tumor.

One particularly aggressive cancer, diffuse large B cell lymphoma (DLBCL) afflicts 25,000 people in the United States each year. As the cancer takes hold, malignant B cells and other immune cells spread throughout the blood stream and lymph organs. As only 40% of patients benefit from chemotherapy, researchers suspected that DLBCL and other lymphomas could be caused by a variety of cell types gone haywire. Finding the original source might mean predicting the best drugs to wipe the cancer out, researchers hoped.

To test this hypothesis, a team led by molecular biologist Louis Staudt of the National Cancer Institute (NCI) in Bethesda, Maryland, sought the origins of tumors from 40 patients with DLBCL and other forms of lymphoma. The researchers studded tiny chips with almost 18,000 different fragments of DNA--pieces of genes known to be expressed in a variety of either normal or cancerous cells. They extracted genetic material from the tumors as well as normal tissue, labeled the molecules with a fluorescent dye, and passed them over the so-called Lymphochips. When the cells' genetic material bumps into the matching anchored fragment on the chips, it sticks and emits a signal.

Almost 2 million signals later, researchers could separate the malignancies into two groups. One had gene expression patterns reminiscent of B cells that live in lymph organs such as the lymph nodes, spleen, or tonsils, suggesting that the metastatic cancer first arose from cells lodged in these organs. The other group pumped out gene products that looked like those from blood-borne immune cells, the team reports in today's Nature. When the researchers checked their results against the medical records of the cancer patients, they found that the majority of the patients with lymph organ cancer cells had responded to chemotherapy, while those with the blood cell form had not.

"It is a beautiful illustration of what technology can do," says molecular biologist Anton Berns, director of the Netherlands Cancer Institute in Amsterdam. The NCI team plans to verify their results in larger groups of patients, possibly tease apart more varieties of lymphoma, and eventually make such chips available for clinical diagnoses. Meanwhile, other researchers have been fast and furiously developing their own versions of the Lymphochip to refine diagnoses of other cancers.