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Lymphochip Reveals Diffuse Large B-Cell Lymphoma Actually Two Forms of Cancer Lymphoma research using gene microarray technology, or "gene chips," has revealed the answer to a long-standing mystery: why chemotherapy has such varied results when treating diffuse large B-cell lymphoma (DLBCL). Out of the 16,000 Americans diagnosed with DLBCL, only forty percent of cases respond favorably to chemotherapy. In fact, it has now been revealed that DLBCL is actually two different cancers, one of which is much more resistant to chemotherapy drugs than the other. The same research has led to the development of a method of analyzing active genes in DLBCL, paving the way for tests to determine a person's receptivity to chemotherapy. The study took thousands of gene samples from over 240 lymphoid biopsies, and used them to create a "lymphochip," a glass chip dotted with over 12,000 gene samples taken from both malignant and benign lymphoid cells. The gene chip is approximately twice the size of a postage stamp. Active cells make RNA copies of DNA called transcripts. These transcripts were gathered and "tagged" with florescent dyes. When these transcripts came into contact with the gene chip, researchers were able to record the patterns and intensity of fluorescence on the lymphochip, indicating which genes were active. Analysis of the information gathered suggested enough variation in the gene's response to chemotherapy to suggest that diffuse large B-cell lymphoma is actually two separate diseases that have been perceived as one by standard diagnostic techniques. Thanks to the research, over six hundred genes were discovered that had a wide range of chemotherapy receptivity. These genes were further pared down to a mere seventeen, which had the most extreme reactions and resistance to chemotherapy. According to Dr. Louis M. Staudt of the National Cancer Institute, these seventeen genes are reliable indicators of the tumors' response to chemo, indicating that the technique may one day be used for routine screening. The discovery that diffuse large B-cell lymphoma is actually two diseases has far-reaching implications for treatment, according to Staudt: "Patients with these two diseases differed significantly in long term survival following standard chemotherapy. These results will have practical importance for cancer patients because the molecular profile of a patient's cancer cells could be used to guide patients towards the therapy that is most likely to be successful for them." Further research will examine even larger amounts of genetic material, in the hope of identifying more subtypes of DLBCL. The eventual hope is to replace the standard staging system for DLBCL, the international prognostic indictor, or IPI, with comprehensive gene pattern screening. Already, indications are that gene patterns may offer a more accurate prognosis: 32 patients involved in the research had poor IPI prognoses. Four of these received chemotherapy based on their gene pattern results, and achieved a complete recovery. Resources Howard Hughes Medical Institution. (2000). "Lymphochip" genetically distinguishes lymphomas. Retrieved May 9, 2003 from www.hhmi.org/news/brown2.html. National Institutes of Health. (2002). Gene expression profiles predict survival of lymphoma patients after chemotherapy. Retrieved May 9, 2003, from www.nih.gov/news/pr/jun2002/nci-19.htm.

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