与多发性内分泌肿瘤 2B 型和散发性甲状腺髓样癌有关的 RET 原癌基因突变

IF 50.5 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Pub Date : 1994-01-27 DOI:10.1038/367375a0

Robert M. W. Hofstra, Rudy M. Landsvater, Isabella Ceccherini, Rein P. Stulp, Tineke Stelwagen, Yin Luo, Barbara Pasini, Jo W. M. Hoppener, Hans Kristian Ploos van Amstel, Giovanni Romeo, Cornells J. M. Lips, Charles H. C. M. Buys

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引用次数: 1098

摘要

多发性内分泌瘤病 2 型（MEN 2）包括三种临床上截然不同的显性遗传癌症综合征。MEN 2A 患者会患上甲状腺髓样癌 (MTC) 和嗜铬细胞瘤。MEN 2B 患者还会出现胃肠道神经节瘤和骨骼异常。在家族性 MTC 中，只有甲状腺受到影响。最近有报道称，RET原癌基因的种系突变与MEN 2A和家族性MTC有关1,2。所有突变都发生在 RET 蛋白胞外域和跨膜域之间过渡点的半胱氨酸残基密码子内。现在，我们发现 MEN 2B 也与 RET 原癌基因的突变有关。在研究的所有九名无关联的 MEN 2B 患者中，都发现了密码子 664 的突变，导致蛋白质酪氨酸激酶结构域中的一个苏氨酸被一个蛋氨酸取代。在 18 例散发性肿瘤中，有 6 例发现了同样的突变。

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A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma

MULTIPLE endocrine neoplasia type 2 (MEN 2) comprises three clinically distinct, dominantly inherited cancer syndromes. MEN 2A patients develop medullary thyroid carcinoma (MTC) and phaeochromocytoma. MEN 2B patients show in addition ganglioneuromas of the gastrointestinal tract and skeletal abnormalities. In familial MTC, only the thyroid is affected. Germ-line mutations of the RET proto-oncogene have recently been reported in association with MEN 2A and familial MTC1,2. All mutations occurred within codons specifying cysteine residues in the transition point between the RETprotein extracellular and transmem-brane domains. We now show that MEN 2B is also associated with mutation of the RET proto-oncogene. A mutation in codon 664, causing the substitution of a threonine for a methionine in the tyrosine kinase domain of the protein, was found in all nine unrelated MEN 2B patients studied. The same mutation was found in six out of 18 sporadic tumours.

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来源期刊

Nature 综合性期刊-综合性期刊

CiteScore

90.00

自引率

1.20%

发文量

3652

审稿时长

3 months

期刊介绍： Nature is a prestigious international journal that publishes peer-reviewed research in various scientific and technological fields. The selection of articles is based on criteria such as originality, importance, interdisciplinary relevance, timeliness, accessibility, elegance, and surprising conclusions. In addition to showcasing significant scientific advances, Nature delivers rapid, authoritative, insightful news, and interpretation of current and upcoming trends impacting science, scientists, and the broader public. The journal serves a dual purpose: firstly, to promptly share noteworthy scientific advances and foster discussions among scientists, and secondly, to ensure the swift dissemination of scientific results globally, emphasizing their significance for knowledge, culture, and daily life.