A MUTATION IN THE RET PROTOONCOGENE ASSOCIATED WITH MULTIPLE ENDOCRINE NEOPLASIA TYPE-2B AND SPORADIC MEDULLARY-THYROID CARCINOMA
A MUTATION IN THE RET PROTOONCOGENE ASSOCIATED WITH MULTIPLE ENDOCRINE NEOPLASIA TYPE-2B AND SPORADIC MEDULLARY-THYROID CARCINOMA
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DOI：
10.1038/367375a0
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发表时间：
1994-01-27
期刊：
影响因子：
64.8
通讯作者：
BUYS, CHCM
中科院分区：
文献类型：
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作者：
HOFSTRA, RMW;LANDSVATER, RM;BUYS, CHCM
多发性内分泌肿瘤2型（MEN 2）包括三种临床不同的，主要遗传的癌症综合征。MEN 2A患者发展为甲状腺髓样癌（MTC）和嗜铬细胞瘤。MEN 2B患者还表现为胃肠道神经节神经瘤和骨骼异常。在家族性MTC中，只有甲状腺受到影响。RET原癌基因的种系突变最近被报道与MEN 2A和家族MTC1,2有关。所有突变都发生在RET蛋白胞外和跨膜结构域之间过渡点指定半胱氨酸残基的密码子内。我们现在表明，MEN 2B也与RET原癌基因的突变有关。在研究的所有9名不相关的MEN 2B患者中，发现密码子664突变导致该蛋白酪氨酸激酶结构域的苏氨酸取代蛋氨酸。在18个散发性肿瘤中，有6个发现了相同的突变。
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 RET protein extracellular and transmembrane 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.