Parathyroid tumor biology in familial multiple endocrine neoplasia type 1: a model for cancer development.

Abstract

Familial multiple endocrine neoplasia type 1 (FMEN 1) is an autosomal dominant disorder characterized by tumors of the parathyroid glands, pancreatic islets, and anterior pituitary. Hyperplasia appears to be the typical histopathological lesion in FMEN 1 endocrine tumors. A circulating mitogen related to basic fibroblast growth factor was active on proliferation of clonal bovine and human parathyroid endothelial cells. Moreover, the FMEN 1 mitogen modulated differentiation of human parathyroid endothelial cell in vitro. All these facts suggested that an extrinsic factor was active on parathyroid endothelial cell growth and differentiation. The FMEN 1 gene maps to chromosome 11q13, and allelic loss in this region has been shown in FMEN 1 parathyroid and pancreatic islet tumors and rarely in anterior pituitary tumors. Together these results support the theory that FMEN 1 parathyroid clonal lesions can develop in the context of generalized hyperplasia. Similarly, in uremic hyperparathyroidism, where parathyroid hyperplasia is thought to be the primary lesion, loss of constitutional heterozygosity for chromosome 11 markers coexists in parathyroid tissue with a polyclonal pattern. Future efforts of scientists working on this genetic disorder will focus on the cloning of the FMEN 1 gene and the development of a suitable bioassay system to study its function.