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, Phosphodiesterase 11A (PDE11A). 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 Gentics, 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.
In the study, the patients’ tumors were made up of cells that were deficient in the enzyme PDE11A. This enzyme halts cyclic nucleotide production in adrenal cells as well as in other kinds of cells in the body. Because they lacked PDE11A, the patients’ adrenal cells had higher levels of cyclic nucleotides. The researchers believe that these higher cyclic nucleotide levels led to the formation of tumors.
The gene for PDE11A contains the information needed to make 4 slightly different forms of the enzyme. The form of the enzyme that was mutated in the patients who took part in the study was found in large amounts in normal adrenal glands and in even larger amounts in normal prostate glands, Dr. Stratakis added. Other forms of PDE11A are found in several other tissues, including the testes, skeletal muscle, and the heart.
Dr. Stratakis noted that although the evidence associating the mutation in the gene for PDE11A to the development of adrenal tumors was very strong, the study was not capable of proving that the mutation actually caused the tumors.
Dr. Stratakis and his colleagues are currently planning studies to determine if differences in the gene for PDE11A might influence an individual’s cancer risk.
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