Eng C, Smith D P, Mulligan L M, Nagai M A, Healey C S, Ponder M A, Gardner E, Scheumann G F, Jackson C E, Tunnacliffe A
Department of Pathology, University of Cambridge, UK.
Hum Mol Genet. 1994 Feb;3(2):237-41. doi: 10.1093/hmg/3.2.237.
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 corresponding germline DNA was wildtype in each case.
三种2型多发性内分泌肿瘤（MEN）综合征的易感基因座已被定位到10q11.2染色体区域，该区域包含RET原癌基因，其编码一种受体酪氨酸激酶。大多数MEN 2A和家族性甲状腺髓样癌是由RET原癌基因细胞外结构域五个半胱氨酸密码子之一内的错义突变引起的。我们现在报告在28个明显不同的MEN 2B家族中的26个家族的种系中存在一个错义突变，该突变导致酪氨酸激酶催化结构域第918位密码子的甲硫氨酸被苏氨酸替代。13例明显散发的甲状腺髓样癌中的5例以及12例明显散发的嗜铬细胞瘤中的1例的DNA含有类似突变，但相应的种系DNA在每种情况下均为野生型。
