Researchers have identified genetic signatures for distinguishing between two types of lymphomas: Burkitt's and diffuse large-B-cell (DLBCL). This distinction is critical because patients with Burkitt's lymphoma require more intense chemotherapy than those with DLBCL. Burkitt's lymphoma is fatal if untreated, and accurate diagnosis will have a major effect on these patients' prognosis.

Burkitt's lymphoma and DLBCL cells look similar under the microscope, and diagnosis can be difficult using conventional pathological methods. A study in the June 8 New England Journal of Medicine describes how gene-expression microarray technology can improve diagnosis of Burkitt's lymphoma.

The study resulted from the collaboration between NCI investigators and the multinational team of researchers in the Lymphoma/Leukemia Molecular Profiling Project. A panel of expert hematopathologists began by reevaluating samples that had been previously diagnosed as Burkitt's lymphoma or atypical Burkitt's lymphoma using available pathological methods. They reclassified a number of samples (originally diagnosed as Burkitt's lymphoma) as DLBCL or high-grade lymphomas, thus demonstrating the difficulty in making an accurate diagnosis.

All samples were then analyzed using DNA gene-expression microarrays. All of the samples classified as Burkitt's lymphoma by the panel were validated as such by gene-expression analysis. However, several samples reclassified as DLBCL by the panel were shown to be Burkitt's by microarray analysis. Overall, the study suggests that 17 percent of the patients who were diagnosed with Burkitt's lymphoma by gene-expression analysis may have been misdiagnosed using standard pathological methods.

"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 Dr. Louis Staudt, deputy chief of the Metabolism Branch at NCI's CCR and study co-leader. "If Burkitt's patients are treated with intensive therapy, there is roughly an 80-percent survival rate. However, if they are misdiagnosed with DLBCL, and treated with lower intensity chemotherapy, the survival rate is reversed to 20 percent or even less."

An editorial, by Drs. Nancy Lee Harris and Sandra J. Horning, concludes that gene-expression analysis identifies a characteristic genetic signature of Burkitt's lymphoma that clearly distinguishes it from DLBCL. Furthermore, they note, the microarray methods seem to "outperform" the expert pathologists.

"Although these results are experimental and the diagnostic techniques are a long way from use on patients, they show the usefulness of gene-expression microarrays for aiding the diagnosis and prognosis of these cancers," said Dr. Staudt. "In the future, knowing the genetic alterations in a cancer will allow us to tailor therapies to match the individual needs of each patient."

By Lynette Grouse