Obara T, Yamashita T, Kanbe M, Ito Y, Egawa S, Yamaguchi K
Tokyo Women's Medical College, Department of Endocrine Surgery.
Nihon Rinsho. 1995 Nov;53(11):2708-15.
Recently, germline mutations in the RET proto-oncogene were found to be associated with multiple endocrine neoplasia (MEN) syndromes, MEN 2A, MEN 2B and Familial medullary thyroid carcinoma (FMTC). In patients with MEN 2A and FMTC different point mutations have been identified in exons 10 and 11 of the cysteine rich regions of RET. Patients with MEN 2B have a single point mutation (ATG to ACG) at codon 918 of RET. Therefore, a direct DNA testing has been developed to provide a highly accurate technique of detecting kindred members who have inherited a specific mutation associated with MEN 2A, MEN 2B or FMTC. In USA and Europe, prophylactic thyroidectomy has been performed on the basis of positive DNA testing, and the presence of a C-cell hyperplasia or a small medullary thyroid carcinoma was confirmed in each patient operated. Through nationwide survey in Japan, 233 patients with MEN 2 syndrome have been identified. They consisted of 180 MEN 2A, 18 MEN 2B, 13 FMTC and 22 unclassified patients. At follow-up, 47% of patients had recurrent medullary thyroid carcinoma and 5.7% of patients died of the disease. Genetic analysis was performed on 15 patients of 6 unrelated families in our series, and the results revealed that germinal mutations of RET as previously reported were also responsible for MEN 2 syndrome in Japanese. DNA analysis and prophylactic thyroidectomy for kindred members at risk for MEN 2 are likely to be beneficial in Japan as well.
最近，人们发现RET原癌基因的种系突变与多发性内分泌腺瘤（MEN）综合征、MEN 2A、MEN 2B以及家族性甲状腺髓样癌（FMTC）有关。在MEN 2A和FMTC患者中，已在RET富含半胱氨酸区域的第10和11外显子中鉴定出不同的点突变。MEN 2B患者在RET的第918密码子处有一个单点突变（ATG突变为ACG）。因此，已经开发出一种直接DNA检测方法，以提供一种高度准确的技术来检测继承了与MEN 2A、MEN 2B或FMTC相关的特定突变的亲属成员。在美国和欧洲，基于DNA检测阳性进行了预防性甲状腺切除术，并且在每个接受手术的患者中均证实存在C细胞增生或微小甲状腺髓样癌。通过在日本进行的全国性调查，已鉴定出233例MEN 2综合征患者。他们包括180例MEN 2A、18例MEN 2B、13例FMTC和22例未分类患者。在随访中，47%的患者出现甲状腺髓样癌复发，5.7%的患者死于该疾病。对我们系列中6个无关家族的15例患者进行了基因分析，结果显示，如先前报道的那样，RET的胚系突变在日本人中也与MEN 2综合征有关。对有MEN 2风险的亲属成员进行DNA分析和预防性甲状腺切除术在日本可能也有益处。
