Frank-Raue K, Höppner W, Buhr H, Herfarth C, Ziegler R, Raue F
Abteilung Endokrinologie und Stoffwechsel, Ruprecht-Karls-Universität Heidelberg.
Dtsch Med Wochenschr. 1997 Feb 7;122(6):143-9. doi: 10.1055/s-2008-1047588.
To determine the importance of the molecular-genetic demonstration of germ-line mutation in the ret protooncogene for therapeutic measures in sporadic and hereditary medullary thyroid carcinoma (MTC).
Several molecular-genetic tests were performed on DNA of 35 families with hereditary and 81 patients with the sporadic form of MTC (isolation of genomic DNA; PCR amplification; DNA sequencing: demonstration of mutation in codon 918 with restriction enzyme FOK 1).
A disease risk was demonstrated in 178 individuals among the 35 families, 159 of whom were investigated by molecular-genetic tests: 84 family members were found to be gene carriers. Germ-line mutation had already been suspected on clinical grounds in 76% of the carriers, 24% being discovered in a presymptomatic stage. Six children among the latter were treated prophylactically by thyroidectomy, histological evidence of C-cell hyperplasia being found in all of them, microcarcinomas in three of the older children. There were four patients among the non-carriers on whom thyroidectomy had been performed previously because of a false-positive pentagastrin-test; but germ-line mutation was now excluded. In one family, with familial MTC in two brothers, no mutation in ret-proto-oncogene has been demonstrated. The members of this family must now, as used to be routine, undergo a pentagastrin-test. Three of the 81 patients with "sporadic" MTC had a germ-line mutation, presumably a new one.
Molecular-genetic tests have further improved the management of families with hereditary MTC and they thus take first place among essential diagnostic procedures. The diagnosis of sporadic MTC can be confirmed by excluding germ-line mutation in the ret-proto-oncogene.
确定在散发性和遗传性甲状腺髓样癌（MTC）中，原癌基因ret生殖系突变的分子遗传学证据对于治疗措施的重要性。
对35个遗传性MTC家族的DNA以及81例散发性MTC患者的DNA进行了多项分子遗传学检测（基因组DNA分离；PCR扩增；DNA测序：用限制性内切酶FOK 1检测密码子918处的突变）。
在35个家族的178名个体中证实存在患病风险，其中159人接受了分子遗传学检测：发现84名家庭成员为基因携带者。在76%的携带者中，临床已怀疑存在生殖系突变，24%是在症状前阶段发现的。后一组中有6名儿童接受了预防性甲状腺切除术，所有儿童均发现有C细胞增生的组织学证据，3名年龄较大的儿童发现有微癌。在非携带者中有4例患者此前因五肽胃泌素试验假阳性而接受了甲状腺切除术；但现在已排除生殖系突变。在一个家族中，两兄弟患有家族性MTC，但未证实ret原癌基因存在突变。该家族成员现在必须像过去常规那样接受五肽胃泌素试验。81例“散发性”MTC患者中有3例存在生殖系突变，可能是新的突变。
分子遗传学检测进一步改善了遗传性MTC家族的管理，因此在重要诊断程序中占据首位。散发性MTC的诊断可通过排除ret原癌基因中的生殖系突变来证实。
