RET oncogene mutations in 75 cases of familial medullary thyroid carcinoma in Japan

The familial form of medullary thyroid carcinoma (MTC) is caused by mutations of the RET protooncogene. We registered 60 multiple endocrine neoplasia (MEN) 2A patients, 12 familial non-MEN medullary carcinoma (FMTC) patients, and three MEN2B patients with a confirmed RET germline mutation. All 60 MEN2A patients had RET mutations in a cysteine-rich domain. Seven of the FMTC patients had a mutation in cysteine-rich domain, and the other five had a mutation in codon 768, which encodes a tyrosine-kinase domain. Two of the MEN2B patients had a mutation in codon 918, and one patient had a double mutation, one in codon 804 and the other in codon 806, both of which are all encoded tyrosine-kinase domain. The genotype–phenotype correlations of our data will allow individualized recommendations for the optimal timing of prophylactic surgery.