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Fox Chase study sheds light on cancer susceptibility and disease involving bone-marrow failure

Defective protein production can occur in cells even when the genes controlling those proteins are normal, according to a new study to be published May 12 in Science. The Fox Chase Cancer Center research sheds light on how genetic defects affecting the control of protein synthesis within cells can increase susceptibility to cancer and other human diseases.

Directed by molecular biologist Davide Ruggero, Ph.D., of Fox Chase Cancer Center's human genetics program, the study attributed the protein defects to a critical glitch in the protein assembly line of ribosomes. This highlights the importance of proteomic research analyzing proteins.

"While defects in a number of genes are known to lead to cancer and disease, this opens up a new avenue of research," Ruggero said. "The DNA may be fine, but now we see another means by which the product it encodes can become defective."

Until now, little has been known about how disease may result from abnormal ribosomes--the protein factories of cells, which use RNA to translate the DNA blueprint into functional proteins. Ruggero's laboratory focuses on understanding control of ribosome activity and how disruptions in RNA translation predispose people to cancer.

His new study shows that specific defects in RNA translation underlie a progressive disease called dyskeratosis congenita. It involves multiple organ systems and includes premature aging and increased susceptibility to cancer. The disease results from a gene mutation, Dkc1, that affects ribosome function.

Dyskeratosis congenita involves abnormal bone marrow leading to anemia, immune deficiency and infections; increased risk of various cancers, including lymphoma; and, starting as early as age 10, abnormalities of skin, nails and mucous membranes that resemble premature aging syndromes. The majority of patients are male.

The Fox Chase researchers used a variety of approaches to study the Dkc1 mutation in c
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Contact: Karen Mallet
Karen.Mallet@fccc.edu
215-728-2700
Fox Chase Cancer Center
11-May-2006


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