Huang H, Qian J, Proffit J, Wilber K, Jenkins R, Smith D I
Department of Laboratory Medicine and Pathology, Mayo Foundation, Rochester, Minnesota, USA.
Oncogene. 1998 May 7;16(18):2311-9. doi: 10.1038/sj.onc.1200202.
FRA7G is an aphidicolin-inducible common fragile site at human chromosomal band 7q31.2. This region is frequently altered in a number of different tumor types including prostate, breast, and ovarian cancer. It has also been hypothesized that this region contains an important tumor suppressor gene which is mutated during the development of these cancers or an oncogene which is amplified. We previously used a FISH-based approach to isolate YAC clones which spanned FRA7G. In this report, we describe the isolation and restriction endonuclease mapping of three overlapping P1 clones which cover FRA7G and the region frequently altered in the different cancers. FISH-based analysis of these clones reveals that aphidicolin-induced breakage in the FRA7G region occurs over a region of at least 300 Kb in length. We have also localized a previously sequenced BAC clone to this region. The sequence obtained from this clone reveals the presence of an endogenous retroviral sequence (HERV-H) in the midst of the FRA7G region as well as sequences with homology to small polydispersed circular DNAs (spcDNAs). Thus for the first two cloned common fragile sites, FRA7G and FRA3B, there is an association with both spcDNAs and hot-spots for viral integration.
FRA7G是位于人类染色体7q31.2带的一个阿非科林诱导型常见脆性位点。在包括前列腺癌、乳腺癌和卵巢癌在内的多种不同肿瘤类型中,该区域经常发生改变。也有人推测,该区域包含一个在这些癌症发生过程中发生突变的重要肿瘤抑制基因,或者一个被扩增的癌基因。我们之前使用基于荧光原位杂交(FISH)的方法分离跨越FRA7G的酵母人工染色体(YAC)克隆。在本报告中,我们描述了三个重叠的P1克隆的分离和限制性内切酶图谱分析,这些克隆覆盖了FRA7G以及在不同癌症中经常发生改变的区域。对这些克隆进行基于FISH的分析表明,FRA7G区域中阿非科林诱导的断裂发生在至少300千碱基(Kb)长的区域。我们还将一个先前已测序的细菌人工染色体(BAC)克隆定位到该区域。从这个克隆获得的序列显示,在FRA7G区域中间存在一个内源性逆转录病毒序列(HERV - H)以及与小分散环状DNA(spcDNA)具有同源性的序列。因此,对于前两个已克隆的常见脆性位点FRA7G和FRA3B,它们都与spcDNA以及病毒整合热点相关。