Mutant cohesin drives chromosomal instability in early colorectal adenomas
Mutant cohesin drives chromosomal instability in early colorectal adenomas
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DOI：
10.1093/hmg/ddu394
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发表时间：
2014-12-20
影响因子：
3.5
通讯作者：
Musio, Antonio
中科院分区：
文献类型：
--
作者：
Cucco, Francesco;Servadio, Adele;Musio, Antonio
染色体错误分离导致染色体不稳定性（CIN），被认为在癌症发展中起作用。由于粘着蛋白在保证正确的染色体分离中起作用，越来越多的数据表明它参与了肿瘤的发生。在一个大型的早期结直肠腺瘤，在结直肠肿瘤发生的早熟步骤，我们确定了11个突变的SMC1A核心粘附素亚基的屏幕。此外，我们对结直肠癌中的SMC1A基因进行了测序，我们只发现了一个突变。最后，在早期腺瘤中鉴定的SMC1A突变和正常人成纤维细胞中野生型SMC1A基因沉默的转染导致CIN。我们的研究结果表明，SMC1A突变从早期腺瘤到结直肠癌逐渐减少，突变导致CIN，这表明突变的粘附素在结直肠癌的发展过程中可能起着关键作用。
Chromosome missegregation leads to chromosomal instability (CIN), thought to play a role in cancer development. As cohesin functions in guaranteeing correct chromosome segregation, increasing data suggest its involvement in tumorigenesis. In a screen of a large series of early colorectal adenomas, a precocious step during colorectal tumorigenesis, we identified 11 mutations in SMC1A core cohesin subunit. In addition, we sequenced the SMC1A gene in colorectal carcinomas and we found only one mutation. Finally, the transfection of the SMC1A mutations identified in early adenomas and wild-type SMC1A gene silencing in normal human fibroblasts led to CIN. Our findings that SMC1A mutations decrease from early adenomas to colorectal cancers and that mutations lead to CIN suggest that mutant cohesin could play a pivotal role during colorectal cancer development.