Clinical presentations and RET protooncogene mutations in seven multiple endocrine neoplasia type 2 kindreds
Clinical presentations and RET protooncogene mutations in seven multiple endocrine neoplasia type 2 kindreds
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DOI：
10.1002/(sici)1097-0142(19961101)78:9
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发表时间：
1996-11-01
期刊：
影响因子：
6.2
通讯作者：
Brennan, MF
中科院分区：
文献类型：
--
作者：
Blank, RD;Sklar, CA;Brennan, MF
背景资料。多发性内分泌腺瘤病2型(MENS 2)是一组相关的常染色体显性遗传癌症综合征，由RET原癌基因突变引起。家族性巨结肠的一个亚组，无节段性巨结肠，也是由该基因突变引起的。方法：作者对6个已建立的男性2个家系和6个明显的散发性疾病患者进行了RET基因第10、11、13和16外显子的突变分析，以确定他们的基因类型和表型。结果：其中一个家系同时携带先天性巨结肠和男性2A，并伴有RET基因620密码子的半胱氨酸到精氨酸替换。一名明显患有散发性疾病的患者被发现有胚系M918T突变。结论已确诊的家族性疾病患者均携带RET病理性种系突变，多条证据支持男性2号综合征肿瘤发生的功能机制增强，而先天性巨结肠无神经节细胞增多的功能机制缺失。作者认为，多次打击机制可以调和单一突变的表面悖论，即在单个患者中同时导致功能障碍的获得和丧失。(C)1996年美国癌症协会。
BACKGROUND. Multiple endocrine neoplasia type 2 (MEN 2) is a group of related autosomal dominant cancer syndromes caused by mutations in the RET protooncogene. A subset of familial Hirschsprung's disease, aganglionic megacolon, is also caused by mutations in this gene.METHODS. The authors performed mutation analysis of exons 10, 11, 13, and 16 of the RET gene in six established MEN 2 kindreds and in six patients with apparent sporadic disease, in order to correlate their genotypes and phenotypes.RESULTS. One of these kindreds carried both Hirschsprung's disease and MEN 2A in conjunction with a cysteine-to-arginine substitution of codon 620 of the RET gene. One patient with apparently sporadic disease was found to have a germline M918T mutation. Patients with confirmed familial disease all carried pathologic germline mutations of RET.CONCLUSIONS. Several lines of evidence support a gain of function mechanism for tumorigenesis in the MEN 2 syndromes but a loss of function mechanism for aganglionosis in Hirschsprung's disease. The authors propose that a multihit mechanism can reconcile the apparent paradox of a single mutation that gives rise to both gain and loss of function disorders in a single patient. (C) 1996 American Cancer Society.