POINT MUTATION WITHIN THE TYROSINE KINASE DOMAIN OF THE RET PROTOONCOGENE IN MULTIPLE ENDOCRINE NEOPLASIA TYPE 2B AND RELATED SPORADIC TUMORS
POINT MUTATION WITHIN THE TYROSINE KINASE DOMAIN OF THE RET PROTOONCOGENE IN MULTIPLE ENDOCRINE NEOPLASIA TYPE 2B AND RELATED SPORADIC TUMORS
复制标题
DOI：
10.1093/hmg/3.2.237
复制
发表时间：
1994-02-01
影响因子：
3.5
通讯作者：
PONDER, BAJ
中科院分区：
文献类型：
--
作者：
ENG, C;SMITH, DP;PONDER, BAJ
三种多发性内分泌肿瘤(MEN)2型综合征的易感基因已被定位于染色体10q11.2区域，该区域含有RET原癌基因，该基因编码受体酪氨酸激酶。大多数男性2A和家族性甲状腺髓样癌是由于RET原癌基因胞外区域的五个半胱氨酸密码子中的一个发生错义突变。我们现在报告一种错义突变，导致酪氨酸激酶催化域918密码子上的苏氨酸替换蛋氨酸，在28个明显不同的男性2B家系中有26个明显不同。13例散发性MTC中有5例和12例散发性嗜铬细胞瘤中有1例存在类似的突变，但相应的生殖系DNA均为野生型。
The susceptibility loci for the three multiple endocrine neoplasia (MEN) type 2 syndromes have been mapped to the region of chromosome 10q11.2 containing the RET proto-oncogene, which codes for a receptor tyrosine kinase. The majority of MEN 2A and familial medullary thyroid carcinoma results from missense mutations within one of five cysteine codons in the extracellular domain of the RET proto-oncogene. We now report a missense mutation, resulting in the substitution of a threonine for a methionine at codon 918 in the tyrosine kinase catalytic domain, in the germline of 26 of 28 apparently distinct families with MEN 2B. DNA from five of 13 apparently sporadic MTC and one of 12 apparently sporadic phaeochromocytomas harboured a similar mutation, but the correspending germline DNA was wildtype in each case.