RET Gene Analysis of 98 Medullary Thyroid Carcinomas

Abstract

The RET gene is a causative gene of multiple endocrine neoplasia type 2A（MEN 2A）, 2B（MEN 2B）, and familial medullary thyroid carcinoma（FMTC）. In this study, we examined RET gene mutation in 98 cases of medullary thyroid carcinomas（MTC）. These patients consisted of 44 familial MTC cases from 23 families, and 54 sporadic MTC cases. RET gene mutations in exons 10, 11 and 13–16 from peripheral blood leukocytes were analyzed by PCR and subsequent automated DNA sequencing. RET gene mutations were found in 23 cases, and mutations were found in codon 611 in 2, 618 in 2, 620 in 3, 634 in 12, 768 in 1, 804 in 2 and 891 in 1, respectively. Seven of 61（11%） apparently sporadic MTC revealed RET gene mutation, which is newly discovered as hereditary MTC. Four of the 7 patients had mutations in exons 13–15, and this region is considered a hotspot occurring in relatively milder MTC. The characteristics of hereditary MTC were younger age at onset of MTC, multiple carcinomas in the thyroid gland, and the association of pheochromocytoma or parathyroid hyperplasia. In conclusion, RET gene screening is a sensitive, specific, and useful method for discriminating gene carriers and non-gene carriers. We recommend RET gene screening for all MTC patients or MTC-suspected patients. Exons 13–15 should be examined in addition to exons 10, 11 and 16.