Molecular basis of hyperparathyroidism

Several advances have been achieved toward an improved understanding of the molecular basis of human parathyroid tumorigenesis. One oncogene involved in the development of parathyroid tumors,PRAD1/cyclin D1, has been discovered and is having a broad impact in oncology and cell-cycle biology. The general genomic locations of several novel putative parathyroid tumor suppressor genes have been identified, providing guideposts toward their specific identification. An already recognized tumor suppressor gene,RB, or a close neighbor on 13q, has been linked to the pathogenesis of parathyroid carcinomas.RET has been centrally implicated in MEN-2A, and investigators are on the verge of isolating theMEN1 gene, both of which are sure to have important basic and clinical implications relevant to parathyroid and other endocrine diseases. Although mutations in theCASR gene itself play a critical role in familial disease, they do not appear to be involved in sporadic parathyroid tumorigenesis, and investigation of genes important for its regulation is warranted. Finally, new molecular genetic approaches will eventually permit the identification of additional parathyroid tumor-provoking genes and will begin to shed light upon other problems in parathyroid biology, such as the relationship between abnormal parathyroid cell proliferation and an altered setpoint in the mechanism linking extracellular calcium concentration to PTH secretion.