Germ line mutation in the RET proto-oncogene associated with familial multiple endocrine neoplasia type 2B: a case report.

Multiple endocrine neoplasia type 2 (MEN 2) is a dominantly inherited cancer syndrome. MEN 2B is characterized by the combined occurrence of medullary thyroid carcinoma (MTC), pheochromocytoma, mucosal neuroma and Marfanoid habitus. Recently, a missense mutation in codon 918 of the proto-RET has been reported in the germ line of apparently distinct families with MEN 2B. In the present paper we first show a familial case of MEN 2B in Japan also to be associated with a germ line mutation in codon 918 of the proto-RET. The mutation was the substitution of a threonine for a methionine in the tyrosine kinase domain of the protein. The germ-like mutations of the proto-RET in MEN 2A and MEN 2B are the first examples of a dominantly acting oncogenic point mutation initiating human hereditary neoplasia.