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Gene Expression Profiling can Diagnose Burkitt's Lymphoma

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Gene expression profiling can accurately distinguish between two types of immune cell tumors - Burkitt's lymphoma and diffuse large B-cell lymphoma (DLBCL) - according to a team of researchers, including several from the National Cancer Institute (NCI), part of the National Institutes of Health (NIH).

Burkitt's lymphoma and DLBCL cells appear similar when viewed under a microscope but correct diagnosis is critical because each cancer requires very different treatments.

Study results appear in the June 8, 2006, issue of the "New England Journal of Medicine". 

"This is an example of how genetic profiling is emerging as a powerful new tool for determining treatment choices," said NIH Director Elias A. Zerhouni, M.D.

"In the future, many tumors will be classified using genetic profiling, and treatments will be tailored to meet the needs of each patient, another example of a more predictive and personalized era of medicine."

"For the first time, we are beginning to have the ability to take microscopically identical tumors from different patients and demonstrate that they are genetically distinct, in order to provide greater certainty about diagnosis and prognosis," said NCI Acting Director John E. Niederhuber, M.D.

"A complete genetic analysis of human cancers will provide us with the ability to match the patient with a highly specific regimen of targeted therapies."

"The value of molecular profiling to accurately diagnosis Burkitt's lymphoma versus DLBCL will have a major impact on patients because the treatment for these two lymphomas is very different," said Louis Staudt, M.D., Ph.D., deputy chief of the Metabolism Branch and head of the Molecular Biology of Lymphoid Malignancies Section in NCI's Center of Cancer Research, as well as research team co-leader.

"If Burkitt's patients are treated with intensive therapy, there is roughly an 80 percent survival rate."

"However, if they are misdiagnosed and treated with the therapy recommended for DLBCL, lower intensity chemotherapy, the survival rate is reversed to 20 percent or even less."

To carry out their study, investigators collected samples of Burkitt's lymphoma from institutions in the United States, Canada and Europe.

A total of 71 samples were obtained from previously untreated patients who had been diagnosed as having Burkitt's lymphoma or atypical Burkitt's lymphoma.

Burkitt's lymphoma samples were then evaluated by a panel of expert hematopathologists using the latest diagnostic methods.

They reclassified the samples into the following categories: Burkitt's lymphoma, atypical Burkitt's lymphoma, DLBCL and high-grade lymphomas.

The review panel reclassified nearly one-third of the samples originally diagnosed as Burkitt's lymphoma, demonstrating the difficulty in making an accurate diagnosis. All samples underwent molecular profiling using DNA microarrays.

Among the samples declared to be Burkitt's lymphoma by the review panel using standard pathological methods, molecular profiling correctly predicted this diagnosis 100 percent of the time.

However, among samples reclassified as DLBCL, molecular profiling identified 35 percent as Burkitt's lymphoma.

Overall, this study suggests that 17 percent of the cases of Burkitt's lymphoma may have been misdiagnosed using standard pathological methods, which would result in inappropriate treatment for these patients.

"The distinction between Burkitt's lymphoma and DLBCL was easy to make based on the molecular profiles," said John Chan, M.D., professor, Nebraska Medical Center in Omaha, Neb., and study co-leader.

"The power of molecular profiling is providing additional information when cases are difficult to diagnose."

"Eventually we hope this type of analysis will help us understand the molecular mechanisms causing this disease and identify novel targets for therapeutic interventions."

This study underscores the value of molecular profiling in diagnosis of Burkitt's lymphoma; however this is an experimental test and will require further development before it is available for clinical use.