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Lack of key enzyme associated with development of rare tumor

Researchers at the National Institutes of Health have discovered that a rare tumor of the adrenal glands appears to result from a genetic deficiency of an important enzyme. The enzyme is one of a class of enzymes involved in halting a cell's response to hormones and appears to stop cells from dividing.

The study, published in Nature Genetics, was conducted by researchers in NIH's National Institute of Child Health and Human Development. The NIH group collaborated with scientists from the Mayo Clinic, the Cochin Institute in Paris, the University of Paris, Ohio State University in Columbus, and the Universitaire Vaudois in Lausanne, Switzerland, in collecting samples from patients with rare adrenal disorders. Scientists from Sapio Sciences in York, Pennsylvania, assisted in the analysis of the data.

In conducting the study, the researchers used gene arrays to analyze the DNA of patients with a rare tumor of the adrenal glands, known as micronodular adrenocortical hyperplasia, explained the study's senior author, Constantine Stratakis, M.D., D(Med)Sc, Chief of NICHD's Section on Endocrinology and Genetics. The researchers also used the technology to analyze samples of the patients' tumors.

The researchers found four patients who had mutant copies of a gene that contains the information for Phosphodiesterase 11A (PDE11A). Phosphodiesterases are a family of enzymes involved in "switching off" a cell's response to hormones, Dr. Stratakis explained.

For a hormone to affect the cell, it must first bind to a molecule, or receptor, on the cell's surface, analogous to how a key fits into a lock. This action triggers the cell to produce substances known as cyclic nucleotides. These function as "second messengers," often stimulating the cell to begin an activity. In the case of adrenal cells, cyclic nucleotides, such as cyclic AMP and cyclic GMP, may stimulate cell growth or other activities. Once the activity has ended, phosphodiesterases
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Source:NIH/National Institute of Child Health and Human Development


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