Rodriguez J A, Barros F, Carracedo A, Mugica-van Herckenrode C M
Department of Cell Biology and Morphological Sciences, School of Medicine and Dentistry, Vizcaya, Spain.
Diagn Mol Pathol. 1998 Oct;7(5):276-82. doi: 10.1097/00019606-199810000-00007.
Alterations in microsatellite sequences have been reported in a variety of human cancers. Microsatellite instability is thought to reflect the inactivation of genes involved in DNA mismatch repair (MMR), which could predispose to the accumulation of further genetic errors in affected cells. Genomic instability in human cancers might also result from the inactivation of cell cycle controls such as the p53-dependent G1 checkpoint that prevents cell replication in response to DNA damage. High-risk human papillomavirus (HPV) is thought to contribute to the development of HPV-associated cancers, including cervical carcinoma, through the interaction of the E6 and E7 viral oncoproteins with two major cell cycle regulatory proteins, namely p53 and the retinoblastoma gene product (pRb). Although the high-risk HPV is prevalent in cervical carcinomas, viral DNA is not detected in a minor proportion of the cases. The HPV infection is insufficient for the development of cervical cancer, which indicates that additional genetic events are involved in the process. This study reports the potential role of MMR gene defects (in addition to or independent of HPV infection) in patients with cervical carcinogenesis. Microsatellite instability and HPV status were analyzed in a series of 54 patients with cervical carcinomas and in two associated cell lines. Microsatellite alterations were examined at 10 loci located in different chromosomes by using semiautomated fluorescent DNA technology and polymerase chain reaction. The HPV types were detected by a general primer polymerase chain reaction method. The results indicate that microsatellite instability is very infrequent in cervical carcinoma and occurs independently of HPV status.
在多种人类癌症中均有微卫星序列改变的报道。微卫星不稳定性被认为反映了参与DNA错配修复（MMR）的基因失活，这可能使受影响细胞中进一步的遗传错误积累。人类癌症中的基因组不稳定性也可能源于细胞周期调控的失活，如p53依赖的G1检查点，它可在DNA损伤时阻止细胞复制。高危型人乳头瘤病毒（HPV）被认为通过E6和E7病毒癌蛋白与两种主要细胞周期调节蛋白，即p53和视网膜母细胞瘤基因产物（pRb）的相互作用，促成HPV相关癌症（包括宫颈癌）的发生。尽管高危型HPV在宫颈癌中普遍存在，但在一小部分病例中未检测到病毒DNA。HPV感染不足以引发宫颈癌，这表明该过程还涉及其他遗传事件。本研究报告了MMR基因缺陷（除HPV感染外或独立于HPV感染）在宫颈癌发生患者中的潜在作用。对54例宫颈癌患者及两个相关细胞系分析了微卫星不稳定性和HPV状态。通过使用半自动荧光DNA技术和聚合酶链反应，在位于不同染色体的10个位点检测微卫星改变。通过通用引物聚合酶链反应方法检测HPV类型。结果表明，微卫星不稳定性在宫颈癌中非常罕见，且其发生与HPV状态无关。
