Parathyroid disorders; genetic/inherited endocrine tumor syndromes

The most longstanding interest of our laboratory has been in the molecular genetic underpinnings of tumors of the endocrine glands. It was in the context of a search for a parathyroid tumor oncogene lying adjacent to a clonal chromosomal breakpoint that we discovered cyclin D1 (PRAD1). Cyclin D1 has proven to play a key role in cell cycle regulation, and has emerged as a major human oncogene, important in multiple types of tumors including breast cancer and B-cell lymphoma. We are currently pursuing a number of approaches, including the use of transgenic mouse models, to learn more about the precise mechanisms by which cyclin D1 exerts its oncogenic effects. In addition to the cyclin D1 work, we are continuing a major initiative seeking additional genes that contribute to endocrine neoplasia. As an example, we identified the HRPT2 (CDC73) gene as a major factor in the development of malignant parathyroid tumors, a finding that carries important clinical implications.

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