Biochemistry of Human Paraganglioma

Researchers in the Maher lab are interested in a fascinating human tumor called paraganglioma. These unusual tumors form from neuroendocrine tissue in the adrenal glands, abdomen or carotid bodies. Strangely, a genetic predisposition to paraganglioma results when a patient inherits genes encoding defects in subunits of the metabolic enzyme succinate dehydrogenase. This enzyme is part of the Krebs cycle in central metabolism.

For unknown reasons, loss of both copies of genes encoding succinate dehydrogenase subunits causes tumors in neuroendocrine tissue. It is paradoxical that a metabolic enzyme defect should cause cancer. Paraganglioma tumors can secrete hormones causing blood pressure problems, or can become malignant and spread in the body as other cancers. Jim Maher's lab is exploring the use of yeast and mouse models of the predisposing genes of paraganglioma to better understand these most unusual tumors. The novel mechanism of carcinogenesis in paraganglioma suggests the possibility of novel approaches to therapy.

Jim Maher, Ph.D., discusses paraganglioma and the Paradifference Foundation, which supports Mayo Clinic research through the generosity of the Gustavsson family and other benefactors.