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June 9, 2006
Gene Expression Profiling Distinguishes Lymphomas
Burkitt’s lymphoma and diffuse large B-cell lymphoma (DLBCL) cells may look similar under a microscope, but each cancer requires different treatments. A multinational team of researchers, including several from NIH’s ×îÐÂÂ鶹ÊÓƵ Cancer Institute, now report that gene expression profiling, a molecular technique that analyzes many genes at once, can distinguish these immune cell tumors more accurately than current diagnostic methods.
Burkitt’s lymphoma and DLBCL are types of non-Hodgkin's lymphomas — malignancies of a type of white blood cell, B lymphocytes. Healthy lymphocytes help destroy bacteria, viruses and other infectious agents invading the body. An estimated 58,800 people will be newly diagnosed with these cancers in the U.S. this year, and about 19,000 will die of them. Both lymphomas can occur in the same age group and patients have similar symptoms, so it’s often difficult for doctors to tell them apart. A correct diagnosis is crucial, however; when Burkitt’s patients are misdiagnosed and treated with the therapy recommended for DLBCL, their survival rate drops from about 80% to 20% or less.
A panel of experts evaluated 71 samples from previously untreated patients who’d been diagnosed with Burkitt’s lymphoma or the related atypical Burkitt’s lymphoma. Using the latest diagnostic methods, they reclassified the samples as Burkitt’s lymphoma, atypical Burkitt’s lymphoma, DLBCL or high-grade lymphoma. The panel reclassified nearly a third of the samples, a sign of how difficult it is to make an accurate diagnosis.
The researchers tested the samples using DNA microarrays to simultaneously measure the activity of over 2,500 genes. The results appear in the June 8, 2006, issue of the New England Journal of Medicine. Among the samples declared to be Burkitt’s lymphoma by the review panel, molecular profiling reached the same diagnosis 100% of the time. However, 17% of the samples that the panel reclassified were revealed to be Burkitt’s lymphoma by molecular profiling. Of those reclassified as DLBCL, molecular profiling showed that 35% were actually Burkitt’s lymphoma. In clinical practice, such misdiagnoses could result in inappropriate treatment for these patients.
This experimental test still requires further development before it’s available for clinical use. In the meantime, researchers see it as a valuable tool to help them understand the molecular mechanisms causing these diseases and uncover novel targets for therapy.