DNA Microarrays Identify Cancer Markers

Researchers employing DNA microarrays have identified a group of 385 genes related to Sezary syndrome, a leukemic form of lymphoma, and have shown that one gene occurs in 70% of patients but not in controls, making it a highly specific marker for the disease.

Sezary syndrome is a leukemic variant of cutaneous T-cell lymphoma, relatively easily treated as a skin disease but often fatal after migration into peripheral blood vessels. Employing advanced DNA screening tools, investigators from the Wistar Institute (Philadelphia, PA, USA) identified 385 genes related to the disease. Genes highly overexpressed in patient samples included Th2 cells--specific transcription factors Gata-3 and Jun B--as well as integrin ß1, proteoglycan 2, the RhoB oncogene, and dual specificity phosphatase 1. Highly underexpressed genes included CD26, Stat-4, and the IL-1 receptors. Message for plastin-T, not normally expressed in lymphoid tissue, was detected only in patient samples and could prove to be a new marker for diagnosis.

The study, published in the June 2, 2003, issue of the Journal of Experimental Medicine, also reported that a panel of eight genes could distinguish Sezary syndrome in patients with as few as 5% circulating tumor cells. Furthermore, a group of 10 genes identified a class of patients who would succumb to the disease within six months of sampling regardless of their tumor burden.

"Our goal in this study was to develop the ability to diagnose cancer at the molecular level using the new technology of DNA arrays,” explained senior author Dr. Louise C. Showe, a professor at The Wistar Institute. "These results demonstrate that we can do that. Cutaneous T-cell lymphoma is very treatable in its earlier stages, but very resistant to treatment later on. One of our hopes is to be able to take what we have learned about Sezary syndrome, the leukemic variant of the disease, and use it to develop an earlier-stage, more-accurate diagnosis of the skin-associated form of this disease, which can be treated so much more effectively.”



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