2A型多发性内分泌腺瘤家系RET原癌基因突变的分子筛查及五肽胃泌素激发试验的临床意义  

Mutation of the RET proto-oncogene in type 2A multiple endocrine neoplasia Chinese families and the application of pentagastrin stimulation test in diagnosis and follow-up

作　　者：姚斌[1] 柳学[2] 陈雄[1] 董婷婷[1] 梁华[1] 翁建平[1] 

机构地区：[1]中山大学附属第一医院内分泌科,广州510080 [2]广东省人民医院

出　　处：《中华内科杂志》2007年第11期914-918,共5页Chinese Journal of Internal Medicine

基　　金：广东省自然科学基金(4009414);广东省科技计划项目(2007B031504004)

摘　　要：目的检测两个2A 型多发性内分泌腺瘤(MEN2A)家系中 RET 原癌基因突变情况,初步探讨两个家系发病的分子机制及了解五肽胃泌素激发试验在 MEN2A 诊疗中的意义。方法提取两个 MEN2A 家系共6名成员外周血基因组 DNA,对 RET 原癌基因21个外显子进行 PCR,PCR 产物进行直接测序,对4例患者测定血降钙素并行五肽胃泌素激发试验。结果两个家系中各有2例患者分别携带 RET 原癌基因外显子11的 C634R 突变和 C634Y 突变。初诊及复发的 MEN2A 患者血清降钙素明显升高(400.5～13 510.7 ng/L,正常值16.6～132.8 ng/L),五肽胃泌素激发后升高更显著(494.1～33901.9 ng/L)。结论本研究中临床诊断为 MEN2A 的家系存在 RET 原癌基因外显子11的 C634位点突变。血降钙素水平及五肽胃泌素激发试验有助于临床诊断和疗效随访。Objective To detect the mutations of RET proto-oncogene in two Chinese families with multiple endocrine neoplasia type 2A （MEN2A） and to study the clinical application of pentagastrin stimulation test in the diagnosis and follow-up of MEN2A. Methods In this study, there were 4 patients clinically diagnosed as MEN2A in the two pedigrees. PCR and direct gene sequencing of PCR products with an automated DNA sequencer were used to scan the entire 21 exons of RET proto-oncogene in the leukocyte DNA of 6 members of the two families. Blood calcitonin was measured and pentagastrin stimulation test carried out in all the 4 clinically diagnosed patients. Results Two missense mutations were detected in exon 11 of the RET proto-oncogene. One was C634R in the 2 patients from one MEN2A family and the other was C634Y in 2 patients from another family. The basal serum calcitonin was very high （400. 5 - 13 510.7 ng/L, normal range 16. 6 - 132. 8 ng/L） in the MEN2A patients and after pentagastrin stimulation the sreum calcitonin level was significantly higher（494. 1 -33 901.9 ng/L）. Conclusions Two mutations （C634R and C634Y） were detected in the patients of two families with MEN2A. Pentagastrin stimulation test was helpful for the diagnosis and follow-up after operative treatment of MEN2A.

关 键 词：多内分泌腺瘤形成2a型 原癌基因 点突变 五肽胃泌素激发试验 

分 类 号：R736[医药卫生—肿瘤]