Hofstra R M, Fattoruso O, Quadro L, Wu Y, Libroia A, Verga U, Colantuoni V, Buys C H
Department of Medical Genetics, University of Groningen, The Netherlands.
J Clin Endocrinol Metab. 1997 Dec;82(12):4176-8. doi: 10.1210/jcem.82.12.4439.
Specific mutations in the ret protooncogene have been found associated with multiple endocrine neoplasia type 2A (MEN 2A) and type 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC). Mutations in one of five cysteine residues in the extracellular domain have been found in over 95% of families with MEN 2A and 88% of families with FMTC. In MEN 2B patients, a specific mutation at codon 918, substituting a threonine for a methionine, has been found in 95% of cases. In FMTC, in addition to the mutations of the extracellular cysteines, three intracellular base pair changes have been reported at codons 768 and 804. Here we describe a novel intracellular mutation in exon 15 of the ret gene that leads to the substitution of an alanine for a serine at codon 891 in a family with medullary thyroid carcinoma. This amino acid change may be important in determining substrate specificity or, alternatively, may play a role in ATP binding.
已发现ret原癌基因中的特定突变与2A型多发性内分泌腺瘤病（MEN 2A）、2B型多发性内分泌腺瘤病（MEN 2B）以及家族性甲状腺髓样癌（FMTC）相关。在超过95%的MEN 2A家族和88%的FMTC家族中，已发现细胞外结构域五个半胱氨酸残基之一发生突变。在MEN 2B患者中，95%的病例在第918密码子处发现了特定突变，即苏氨酸替代甲硫氨酸。在FMTC中，除了细胞外半胱氨酸的突变外，还报道了第768和804密码子处的三个细胞内碱基对变化。在此，我们描述了ret基因第15外显子中的一种新型细胞内突变，该突变导致一个甲状腺髓样癌家族中第891密码子处的丝氨酸被丙氨酸替代。这种氨基酸变化可能在决定底物特异性方面很重要，或者可能在ATP结合中发挥作用。
