Bolino A, Schuffenecker I, Luo Y, Seri M, Silengo M, Tocco T, Chabrier G, Houdent C, Murat A, Schlumberger M
Laboratorio di Genetica Molecolare, Istituto G. Gaslini, Genova, Italy.
Oncogene. 1995 Jun 15;10(12):2415-9.
RET is a receptor tyrosine kinase gene which is responsible for three different inherited cancer syndromes namely multiple endocrine neoplasia type 2A (MEN 2A), type 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC) as well as for Hirschsprung disease (HSCR), a congenital disorder affecting the intestinal motility. Germ-line mutations in the RET exons 10 and 11 were demonstrated in the majority of the MEN 2A and FMTC patients. On the other hand, one codon of RET exon 16 is preferentially changed in MEN 2B patients. Recently, a germ-line mutation in the exon 13 was described in one FMTC family as well as in four sporadic MTCs. In the present study, we observed the same exon 13 mutation in two FMTC families. In addition, we identified a previously unreported substitution of RET exon 14 in two unrelated FMTC families. Both mutations segregate with the disease in these four FMTC families and involve the tyrosine kinase domain of RET. Haplotype analysis using polymorphic markers tightly linked to the RET gene indicates that in each pedigree the mutation arose as an independent event.
RET是一种受体酪氨酸激酶基因，它导致三种不同的遗传性癌症综合征，即2A型多发性内分泌腺瘤病（MEN 2A）、2B型（MEN 2B）和家族性甲状腺髓样癌（FMTC），以及先天性巨结肠病（HSCR），一种影响肠道蠕动的先天性疾病。大多数MEN 2A和FMTC患者的RET基因第10和11外显子存在种系突变。另一方面，MEN 2B患者中RET基因第16外显子的一个密码子优先发生改变。最近，在一个FMTC家族以及四个散发性甲状腺髓样癌（MTC）中发现了第13外显子的种系突变。在本研究中，我们在两个FMTC家族中观察到相同的第13外显子突变。此外，我们在两个不相关的FMTC家族中发现了RET基因第14外显子一个以前未报道的替换。这两种突变在这四个FMTC家族中均与疾病共分离，并且涉及RET的酪氨酸激酶结构域。使用与RET基因紧密连锁的多态性标记进行单倍型分析表明，在每个家系中，突变都是作为一个独立事件出现的。
