家系多发性内分泌肿瘤诊治及RET原癌基因突变的研究

目的 探讨多发性内分泌肿瘤( MEN)的临床诊治特点及RET原癌基因检测的临床意义。 方法 家系中诊断MEN患者3例，男1例，50岁；女2例，38岁和33岁。2例行双侧肾上腺全切术：1例行保留双侧肾上腺的肾上腺嗜铬细胞瘤切除术。3例均行甲状腺全切+颈部淋巴结清扫术。家系中12名成员抽血，提取基因组DNA，对RET原癌基因第10、11外显子行PCR检测，对PCR产物进行基因测序。 结果 3例患者病理诊断为双肾上腺嗜铬细胞瘤+甲状腺髓样癌。38岁、33岁女患者及男患者术后分别随访5年、4年2个月、1年6个月，均无肿瘤复发或转移。3例均检测到RET原癌基因第11外显子TGC→CGC( Cys634 Arg)错义突变，使编码氨基酸由半胱氨酸变成精氨酸。家系其他成员中发现2名该突变基因携带者。 结论 对MEN高危家族的RET原癌基因检测筛选及早期手术干预是治愈MEN的关键。

RET proto-oncogene mutation analysis in a pedigree with multiple endocrine neoplasia 2A

Objective To discuss the clinical diagnosis and treatment of multiple endocrine neoplasia ( MEN ) 2A, and report the mutation of the RET proto-oncogene in a pedigree of three patients with MEN 2A.Methods Bilateral adrenalectomy was performed on two of the three patients with hypertension and bilateral adrenal-conserving adrenal pheochromocytoma resection was performed on the other patient. All three patients were treated by total thyroidectomy and neck lymphadenectomy. Twelve family members were recruited to the study. Peripheral blood was collected and total genomic DNA was prepared for polymerase chain reaction (PCR). PCR products of exon 10 and exon 11 of the RET proto-oncogene were purified and a direct DNA sequence analysis was performed.Results The pathological diagnosis of the specimens was bilateral adrenal pheochromocytoma and medullary thyroid carcinoma in all the three patients. There was no tumor recurrence or distant metastasis after 1.5 - 5 years of follow-up. A missense mutation of TGC (Cys)to CGC (Arg) at codon 634 in exon 11 of the RET proto-oncogene was detected in all three patients. Genetic screening identified two mutation carriers in the other members of this pedigree.ConclusionGenetic mutation screening and surgical intervention may be helpful to the members of high-risk families.