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Gene Defects Determine Susceptibility to Cancer and Bone Marrow Failure

A new study has now highlighted that certain gene defects that control of protein synthesis can either increase or decrease an individual's susceptibility to cancer and other diseases. //Surprisingly, such genetic mechanisms can be responsible for cancer although the protein levels are normal, reveals the study that has been published in the journal, Science.

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 cells f
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