RET Proto-Oncogene and Thyroid Cancer

TheRET proto-oncogene has not only conclusively been identified as responsible for the three subtypes of the inherited cancer syndrome multiple endocrine neoplasia type 2 (MEN-2) but also shown to be involved in the molecular evolution of sporadic medullary and papillary thyroid carcinoma as well as Hirschsprung’s disease. A variety of recent studies have elucidated the pathophysiological mechanisms leading to neoplastic disease and we now understand that dominant activating germline mutations lead to MEN-2A, MEN-2B, and familial MTC; somatic mutations to sporadic medullary thyroid carcinoma;RET rearrangements to papillary thyroid carcinoma; and inactivating alterations to Hirschsprung's disease. The clinical significance, however, ofRET alterations especially in sporadic thyroid tumors is still controversial and therapeutic concepts in MEN-2 gene carriers only start to emerge. This article is a short summary of the recent findings on the structure and physiology of theRET proto-oncogene and its role in familial and sporadic thyroid cancer. This article was presented in part at the Endocrine Pathology Society Companion Meeting of the USCAP in Orlando, FL, March 1, 1997.