Evaluation of germline sequence variants of GFRA1, GFRA2, and GFRA3 genes in a cohort of Spanish patients with sporadic medullary thyroid cancer.
Evaluation of germline sequence variants of GFRA1, GFRA2, and GFRA3 genes in a cohort of Spanish patients with sporadic medullary thyroid cancer.
复制标题
对西班牙散发性甲状腺髓样癌患者队列中 GFRA1、GFRA2 和 GFRA3 基因种系序列变异的评估。
DOI：
10.1089/105072502320908367
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Antiñolo,Guillermo
中科院分区：
文献类型：
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作者：
Borrego,Salud;Fernández,RaquelM;Dziema,Heather;Japón,MiguelA;Marcos,Irene;Eng,Charis;Antiñolo,Guillermo
散发性甲状腺髓样癌（sMTC）的病因仍不清楚。虽然 RET 原癌基因中的种系功能获得性突变会导致遗传性 MTC，但已在不同数量的 sMTC 中描述了体细胞 RET 突变。迄今为止，S836S ofRET 是在多个欧洲队列中发现的唯一与 sMTC 相关的变体。由于 RET 变异似乎与 MTC 相关，因此编码 RET 共同受体的基因变异可能在 sMTC 的发病机制中发挥作用，这似乎是合理的。最近，我们在德国 sMTC 系列中描述了编码 RET 受体 GFRα1 的基因中两个可能的低外显率易感性等位基因，-193C > G 和 537T > C。在这项研究中，我们对 51 名西班牙 sMTC 和 100 名正常对照的 GFRA1-3 基因内的 9 个多态性进行了基因分型。我们的结果表明，当西班牙 sMTC 患者与对照组进行比较时，没有发现统计学意义。结合德国 sMTC 系列的观察结果，目前的研究结果表明 GFRA1-193C > G 和 537T > C 可能与其他导致德国疾病的基因座存在连锁不平衡，并具有创始人效应。 或者，综合观察结果也可能表明，如果多态性确实发挥作用，那么影响很小。
The etiology of sporadic medullary thyroid carcinoma (sMTC) remains elusive. While germline gain-of-function mutations in theRETproto-oncogene cause hereditary MTC, somaticRETmutations have been described in a variable number of sMTC. So far, S836S ofRET, is the only variant whose association with sMTC has been found in several European cohorts. BecauseRETvariants seem to be associated with MTC, it is plausible that variants in genes encoding forRETcoreceptors may play a role in the pathogenesis of sMTC. Recently, we described two possible low penetrance susceptibility alleles in the gene encodingRETcoreceptor GFRα1, -193C > G and 537T > C, in a German series of sMTC. In this study, we have genotyped nine polymorphisms withinGFRA1-3genes for 51 Spanish sMTC, and 100 normal controls. Our results show that no statistical signification was found when Spanish sMTC patients were compared to controls. Taken together with the observations in the German sMTC series, the present findings suggest thatGFRA1-193C > G and 537T > C could be in linkage disequilibrium with other loci responsible for the disease with a founder effect in Germany. Alternatively, the combined observations might also suggest that, if indeed the polymorphisms are functional, the effect is small.