Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A

IF 50.5 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Pub Date : 1993-06-03 DOI:10.1038/363458a0

Lois M. Mulligan, John B. J. Kwok, Catherine S. Healey, Mark J. Elsdon, Charis Eng, Emily Gardner, Donald R. Love, Sara E. Mole, Julie K. Moore, Laura Papi, Margaret A. Ponder, Hakan Telenius, Alan Tunnacliffe, Bruce A. J. Ponder

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引用次数: 1820

Abstract

MULTIPLE endocrine neoplasia type 2A (MEN 2A) is a dominantly inherited cancer syndrome that affects tissues derived from neural ectoderm. It is characterized by medullary thyroid carcinoma (MTC) and phaeochromocytomal. The MEN2A gene has recently been localized by a combination of genetic and physical mapping techniques to a 480-kilobase region in chromosome 10qll.2 (refs 2,3). The DNA segment encompasses the RET proto-oncogene, a receptor tyrosine kinase gene expressed in MTC and phaeochromocytoma and at lower levels in normal human thyroid4. This suggested RET as a candidate for the MEN2A gene. We have identified missense mutations of the RET proto-oncogene in 20 of 23 apparently distinct MEN 2A families, but not in 23 normal controls. Further, 19 of these 20 mutations affect the same conserved cysteine residue at the boundary of the RET extracellular and transmembrane domains.

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多发性内分泌肿瘤 2A 型中 RET 原癌基因的种系突变

多发性内分泌瘤病 2A 型（MEN 2A）是一种显性遗传癌症综合征，会影响神经外胚层的组织。其特征是甲状腺髓样癌和辉色细胞瘤。最近，通过遗传和物理绘图技术的结合，MEN2A 基因被定位到染色体 10qll.2 中的一个 480 千碱基区域（参考文献 2,3）。该 DNA 片段包含 RET 原癌基因，这是一种在 MTC 和嗜铬细胞瘤中表达的受体酪氨酸激酶基因，在正常人甲状腺中的表达水平较低4。这表明 RET 是 MEN2A 基因的候选基因。我们在 23 个明显不同的 MEN 2A 家族中的 20 个家族中发现了 RET 原癌基因的错义突变，但在 23 个正常对照组中却没有发现。此外，这 20 个突变中有 19 个影响到 RET 细胞外结构域和跨膜结构域边界上的相同保守半胱氨酸残基。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.