Gene Mutation That Increases the Risk of Chronic Lymphocytic Leukaemia Found

by Medindia Content Team on  June 1, 2007 at 6:32 PM Cancer News   - G J E 4
Gene Mutation That Increases the Risk of Chronic Lymphocytic Leukaemia Found
Scientists at Ohio State University Comprehensive Cancer Center have discovered an inherited gene mutation that makes a person more vulnerable to chronic lymphocytic leukaemia (CLL).

The study shows that the inherited mutation greatly reduces the gene's protective activity. Furthermore, a second kind of change occurs later that turns the gene off altogether, leading to leukemia. This latter alteration is a chemical change that is not inherited.

The finding could help to identify people at risk for chronic leukaemia, and also provide new insights into the process of natural cell death. They may even lead to new strategies for treating the disease.

The study was conducted by a team of researcher including John C. Byrd, Albert de la Chapelle, Christoph Plass and colleagues at the Ohio State University Comprehensive Cancer Center.

CLL is the most common form of adult leukaemia. It is slightly more common in men than women, and typically strikes people who are in their 50s, 60s and 70s. About 90 percent of CLL cases are sporadic, that is, they have no genetic component.

As part of the study, researchers identified the mutation by testing a family in which the father, four sons, a grandson and a distant female relative who developed this form of leukaemia through mutation found in a gene called DAPK1, which normally helps trigger the death of cells before they become cancerous.

The chemical change is called DNA methylation. Healthy cells use this process to silence unneeded genes. But abnormal DNA methylation can turn off genes that control cell growth, and that lead to tumor growth.

"Our findings identify for the first time a gene that appears to be associated with hereditary CLL," Byrd said.

"They also show the importance of the gene in the pathogenesis of CLL, and direct us to target this gene with therapies that might re-activate it," Byrd added.

The findings also provide evidence that some genes might contribute to cancer even when they are not silenced entirely.

"This inherited change is remarkably subtle. It does not shut down the gene, but just lowers its expression somewhat. Recently, many cancer geneticists have come to believe that such subtle changes are common causes of cancer, and this is one of the first, strong examples of that principle," Chapelle.

"Our findings show that it's important to look for both genetic and epigenetic alterations when identifying problem genes," Plass said.

The findings of the study will be published in the June issue of the journal Cell.

Source: ANI

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