多发性内分泌腺瘤2A型一家系中的原癌基因RET p．C618R突变  

Multiple endocrine neoplasia type 2A caused by a p. C618R RET proto-oncogene mutation in a Chinese pedigree

作　　者：陈振光[1] 戚晓平[1] 费军[1] 余秀华[2] 赵燕[3] 赵坚强[4] 金杭阳[1] 王金泉[5] 应荣彪 张咸宁[3] 

机构地区：[1]解放军第一一七医院肿瘤泌尿外科,杭州310004 [2]解放军第一一七医院超声科,杭州310004 [3]浙江大学医学院生化和遗传学系 [4]浙江省肿瘤医院头颈外科 [5]解放军第一一七医院病理科,杭州310004 [6]浙江省台州市肿瘤医院肿瘤外科

出　　处：《中华医学遗传学杂志》2014年第3期348-351,共4页Chinese Journal of Medical Genetics

基　　金：南京军区医学科技创新课题基金重点项目（092038,102036）

摘　　要：目的探讨多发性内分泌腺瘤2A型（multiple endocrine neoplasia type2A，MEN2A）的临床特点及RET原癌基因检测的意义。方法对1个MEN2A家系进行系统的临床家系调查和种系水平的RET基因检测。结果基因检测该家系5位成员中3例存在RET基因p．C618R杂合错义突变，与临床完全相符。男1例，女2例。首次诊断年龄分别为21岁、26岁和36岁。甲状腺髓样癌最大直径分别为2．2cm、2．5cm和3．9cm。36岁女患者首次手术仅接受了右侧甲状腺全切＋右颈部淋巴结清扫术，4年后先、后接受了左侧肾上腺嗜铬细胞瘤切除术、左侧甲状腺全切＋左侧颈部淋巴结清扫术；21岁男患者接受了右侧甲状腺全切＋右侧颈部改良淋巴结清扫术。2例患者分别随访146、26个月，降钙素仍均升高伴双侧颈部淋巴结肿大或伴左侧甲状腺占位。26岁女患者伴双侧甲状腺占位和降钙素升高，但拒绝治疗。结论结合临床筛查和RET基因检测，有利于MEN2A的及早诊断和规范化治疗，提高远期治愈率。Objective To explore the clinical characteristics and significance of RET proto-oncogene screening in multiple endocrine neoplasia type 2A（MEN2A）. Methods Comprehensive medical history was obtained for 5 members from a 3-generation family from southern China. Clinical investigations have included biochemical testing, imaging, and screening of germline RET proto-oncogene mutations. Results Genetic screening has revealed a missense mutation at codon 618（TGC〉CGC） of exon 10 in 3 patients（p. C618R）, which was consistent with their clinical manifestations. For the3 individuals, the age at diagnosis was 21, 26 and 36, and the maximum diameter of medullary thyroid cai＇cinoma was 2.2, 2.5 and 3.9 cm, respectively. The 36-year-old female patient initially underwent right total thyroidectomy plus right neck lymph node dissection. Four years later, she again underwent left adrenal tumorectomy and left total thyroidectomy plus left neck lymph node dissection. The 21-year-old male patient underwent right total thyroidectomy plus right modified neck dissection. The follow-up was respectively 146 and 26 months following the initial operation. Two patients still presented elevated calcitonin and had bilateral neck lymph node masses and/or left thyroid masses on imaging examination. The 26-year-old female patient, who presented bilateral thyroid masses and elevated calcitonin, has refused thyroidectomy. Conclusion Combined family survey and RET gene screening can facilitate early diagnosis and surgical treatment to improve the prognosis.

关 键 词：多发性内分泌腺瘤2型 甲状腺髓样癌 肾上腺嗜铬细胞瘤 RET原癌基因 点突变 

分 类 号：R736[医药卫生—肿瘤]