Evidence that instability within the FRA3B region extends four megabases
Evidence that instability within the FRA3B region extends four megabases
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DOI：
10.1038/sj.onc.1205950
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发表时间：
2002-12-12
期刊：
影响因子：
8
通讯作者：
Smith, DI
中科院分区：
文献类型：
--
作者：
Becker, NA;Thorland, EC;Smith, DI
FRA3B是人类染色体3p14.2带中表达最频繁的常见脆性位点，在包括宫颈癌在内的许多不同的肿瘤中经常缺失。以前的报告表明，在1.5Mb脆性组氨酸三联体(FHIT)基因跨越的500kb范围内，发生了由Aphidiclin诱导的FRA3b不稳定性。最近，一个HPV16宫颈肿瘤整合，2Mb着丝粒到已公布的FRA3b区域，已经被发现。基于FISH的分析和BAC跨越整合已经证明这种整合发生在FRA3B的不稳定区域内。这些数据表明，不稳定的FRA3B区域比以前报道的要大得多。基于FISH的分析允许对与FRA3B相关的不稳定性进行完整的表征。该分析表明，脆弱性延伸到4Mb。在这个区域内共有五个基因，包括FHIT。对一组宫颈肿瘤细胞系的FRA3B基因表达分析显示，FRA3B内的五个基因中有三个基因被异常调控。对FRA3B以外的基因进行的类似分析表明，周围的基因没有异常表达。这些数据提供了额外的支持，即与CFS相关的不稳定区域及其包含的基因可能在癌症的发展中发挥重要作用。
FRA3B is the most frequently expressed common fragile site localized within human chromosomal band 3p14.2, which is frequently deleted in many different cancers, including cervical cancer. Previous reports indicate aphidicolin-induced FRA3B instability occurs over similar to500 kb which is spanned by the 1.5 Mb fragile histidine triad (FHIT) gene. Recently an HPV16 cervical tumor integration, 2 Mb centromeric to the published FRA3B region, has been identified. FISH-based analysis with a BAC spanning the integration has demonstrated this integration occurs within the FRA3B region of instability. These data suggest that the unstable FRA3B region is much larger than previously reported. FISH-based analysis of aphidicolin-induced metaphase chromosomes allowed for a complete characterization of instability associated with FRA3B. This analysis indicates that fragility extends for 4 Mb. Within this region are a total of five genes, including FHIT. FRA3B gene expression analysis on a panel of cervical tumor-derived cell lines revealed that three of the five genes within FRA3B were aberrantly regulated. A similar analysis of genes outside of FRA3B indicated that the surrounding genes were not aberrantly expressed. These data provide additional support that regions of instability associated with CFSs and the genes contained within them, may play an important role in cancer development.