五个多发性内分泌肿瘤2B家系的临床分析和RET原癌基因突变研究  

Clinical analysis and research in SET proto-oncogene mutation in five MEN2B pedigrees

作　　者：周瑜琳[1] 赵咏桔[1] 成昌友 赵铁耘[3] 殷志强[4] 洪洁[1] 张翼飞[1] 顾丽群[1] 汤正义[1] 崔斌[1] 宁光[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院内分泌代谢病科,上海市内分泌代谢病临床医学中心,上海市内分泌代谢病研究所,200025 [2]连云港赣渝县人民医院内分泌科 [3]华西医科大学附属第一医院内分泌科 [4]上海仁济医院泌尿外科

出　　处：《中华内分泌代谢杂志》2006年第6期549-553,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：上海市科委资助项目(24119054)

摘　　要：目的研究5例多发性内分泌肿瘤(MEN)2B患者及其家族成员的临床表型和PET原癌基因突变。方法提取5例有典型临床表型的MEN2B患者及其23名家族成员外周血基因组DNA,对RET原癌基因第8、10、11、13、14、15、16外显子进行PCR产物直接测序。结果MEN2B临床表型和基因突变仅存在于5例先证者中,其家族成员均未发现；5例患者确诊MEN2B时的甲状腺髓样癌(MTC),类马凡体型,唇舌的黏膜神经瘤,眼部异常,肠道异常和嗜铬细胞瘤(PCC)的发生数分别为5、5、5、4、3和3；其MTC和PCC的发病年龄分别为(20．0±8．1)岁和(28．3±2．5)岁；RET基因突变均为第16外显子的M918T。结论本组MTC和PCC的平均发病年龄均晚于国外相关报道,且PCC发病晚于MTC；MEN2B其他相关临床症状的发生率大于国外报道,考虑与MEN2B确诊较晚有关。本组MEN2B先证者发生RET突变的家系比例(100%)要明显高于国外的相关报道(50%),且均为RET原癌基因的M918T单一突变。Objective To investigate the phenotype and the mutation of RET proto-oncogene in five patients with multiple endocrine neoplasia 2B （MEN2B） and their family members. Methods Five patients with typical phenotype of MEN2B and their 23 family members were recruited. Total genomic DNA was extracted from their peripheral blood for PCR. PCR products of exon 8, 10, 11, 13, 14, 15 and 16 of the RET proto-oncogene were purified and direct sequencing was performed. Results The phenotype and gene mutation of MEN2B only occurred in five patients with MEN2B and none of their family members; The prevalences of medullary thyroid carcinoma （MTC）, marfanoid habitus, neuroma of tongue and lips, ocular and intestinal disorders and pheochromocytoma （PCC） were 100% （5/5）, 100% （5/5）, 100% （5/5）, 80% （4/5）, 60% （3/5） and 60% （3/5） respectively when MEN2B was diagnosed. When MTC and PCC occurred, the age was （20.0±8.1 ）years old and （28.3±2.5）years old. Only M918T of exon 16 in RET proto-oncogene was found. Conclusion The mean onset age of MTC and PCC in this study is older than that reported abroad while PCC happened after MTC; The prevalences of other MEN2B clinical manifestations are higher than those reported abroad probably due to later diagnosis of MEN2B. The percentage of the proband getting the RET mutation（ 100% ） is obviously higher than that reported abroad（50% ）. Only single RET proto-oneogene mutation （M918T） is found in this study.

关 键 词：多发性内分泌瘤病2b型 甲状腺肿瘤 癌 髓样 RET原癌基因 

分 类 号：R736[医药卫生—肿瘤]