Germline RET mutations in exons 10 and 11: An Iranian survey of 57 medullary thyroid carcinoma cases

Medullary Thyroid Carcinoma (MTC) occurs in either sporadic or hereditary forms. The susceptibility gene for hereditary MTC is the RET proto-oncogene. The aim of this study was to evaluate the prevalence of common germline RET mutations in exons 10 and 11 among Iranian MTC patients. 57 non-related MTC patients were examined in this survey (F: M=1.2:1.0, 40.0±11.5 years). Genomic DNA was extracted from their peripheral blood samples and exons 10 and 11 of the RET proto-oncogene were amplified using polymerase chain reaction (PCR). The PCR products were then digested by specific restriction enzymes and the Restriction Fragment Length Polymorphism (RFLP) patterns were analyzed for common RET mutations in exons 10 and 11. Only the MEN2A patient displayed a C634W mutation in exon 11. Three of the six first-degree relatives of the MEN2A evaluated patient had the same mutation. Among apparently sporadic MTC patients (53 cases), one patient showed a C620R mutation in exon 10 and two other patients displayed C634Y mutations in exon 11 of the RET proto-oncogene. Neither were the only MEN2B patient nor the two FMTC patients found to carry germline mutations in exons 10 and 11 of the RET proto-oncogene. It seems that the prevalence of germline RET mutations in exons 10 or 11 is prominent (5.7%) among Iranian, apparently sporadic, MTC patients. We conclude that a routine germline mutation analysis of the RET proto-oncogene should be advised for apparently sporadic MTC patients. Hereditary forms of MTC require a more extended investigation for RET mutations.