CLINICAL AND MOLECULAR ASPECTS OF MULTIPLE ENDOCRINE NEOPLASIA

The multiple endocrine neoplasias (MEN) include three autosomal domina nt disorders: MEN1, MEN2A, AND MEN2B. MEN1 is characterized by neoplas ia of the anterior pituitary, pancreas, and parathyroid glands; the di sorder has been mapped to 11q13. MEN2A and MEN2B are characterized by medullary thyroid cancer and pheochromocytoma. Parathyroid abnormaliti es may also be present in MEN2A, while MEN2B includes mucosal neuromas and skeletal abnormalities. MEN2A and MEN2B are due to mutation in th e RET proto-oncogene on chromosome 10q11.2. The identification of the causative mutations in RET has resulted in the availability of molecul ar genetic testing for MEN2A and MEN2B. DNA-based testing has allowed for significant improvement in the clinical management of MEN2 kindred neoplasias. It was recently reported that a phenotypically distinct d isorder, Hirschsprung disease, is also due to mutation in RET.