Identification of the germline mutation in the RET proto-oncogene is important for the diagnosis of hereditary medullary
thyroid carcinoma (MTC). Hereditary forms account for approximately 25%-30% of all cases of MTC. The objective of this study was to evaluate the prevalence of the RET mutation and the genotype-phenotype relation in Korean patients with MTC. Genomic DNAs were obtained from 33 patients with MTC (M:F = 10:23, 39.8 +/- 12.0 years) who underwent total
thyroidectomy between 1997 and 2003 at the Samsung Medical Center. Exons 10, 11, 13, 14, 15 and 16 of the RET proto-oncogene were amplified with specific primers using polymerase chain reaction (PCR). Sequence analysis was performed on the polymerase chain reaction (PCR) product using an automatic sequence analyzer. Nine of the 33 patients (M:F = 3:6, 33.3 +/- 10.0 years) were identified as having RET mutations. Six patients had
multiple endocrine neoplasia (
MEN) 2A and one had
familial medullary thyroid carcinoma (FMTC). The remaining two patients were thought to have sporadic MTC. Five of the patients with
MEN 2A had RET mutations in
codon 634 of exon 11 (3 patients, C634Y; 2 patients, C634R) and the other patient with
MEN 2A had a RET mutation in
codon 618 of exon 10 (C618R). The patient with FMTC had a mutation in
codon 634 (C634W). The two patients with sporadic MTC had RET mutations in
codon 634 (1 patient, C634Y; 1 patient, C634S). We were not able to identify any genotype-phenotype relations because of the limited number of patients. Twenty-seven percent (9/33) of the patients with MTC in this study had RET mutations. Taking other studies into account, 77% (10/13) of Korean families with
MEN 2A, including 7 other families in three reports from Korea, had RET mutations in
codon 634 (5 families, C634Y; 4 families, C634R; 1 family, C634W), and 23% (3/13) had RET mutations in
codon 618 (2 families, C618R; 1 family, C618S). RET proto-oncogene mutations were restricted to
codon 634 and 618 in Korean families with
MEN 2A.