Genomic instability at simple repeated sequences has been observed in various types of human cancers and is considered an important mechanism in tumorigenesis. Alterations at microsatellite loci have been reported scattered throughout the genome. Recently, the transforming growth factor-beta receptor type II (TGF-beta RII) and the insulin-like growth factor II receptor (IGF-IIR) genes were shown to have inactivating mutations within coding microsatellite sequences. The demonstration of mutations in two growth regulatory genes supports the idea that other regulatory genes with repeat sequences may also be targets in tumours with defective mismatch repair. We examined genes involved in tumour suppression, cell adhesion and cell cycle regulation for mutations at small repeat sequences in replication error positive gastrointestinal cancers. Several polymorphisms were found which exhibited instability, but no other instability was present in the regions examined.

译文

在各种类型的人类癌症中已经观察到简单重复序列的基因组不稳定性,并且被认为是肿瘤发生的重要机制。据报道,微卫星基因座的改变分散在整个基因组中。最近,研究表明转化生长因子β受体II型(TGF-βRII)和胰岛素样生长因子II受体(IGF-IIR)基因在编码微卫星序列中具有失活突变。两个生长调节基因突变的证明支持了这样的想法,即具有重复序列的其他调节基因也可能是错配修复缺陷的肿瘤的靶标。我们检查了涉及复制抑制阳性胃肠道癌中小重复序列突变的肿瘤抑制,细胞粘附和细胞周期调控的基因。发现了几个表现出不稳定性的多态性,但在检查的区域中没有其他不稳定性。

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