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
摘要
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。
Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A
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.
期刊介绍:
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