Wang L, Darling J, Zhang J S, Qian C P, Hartmann L, Conover C, Jenkins R, Smith D I
Department of Laboratory Medicine and Pathology, Mayo Clinic/Foundation, Rochester, Maine 55902, USA.
Oncogene. 1998 Feb 5;16(5):635-42. doi: 10.1038/sj.onc.1201576.
FRA3B at human chromosomal band 3p14.2 is the most active common fragile site in the human genome. The molecular mechanism of fragility at this region remains unknown but does not involve expansion of a trinucleotide or minisatellite repeat as has been observed for several of the cloned rare fragile sites. Deletions and rearrangements at FRA3B have been observed in a number of distinct tumors. The recently identified putative tumor suppressor gene FHIT spans FRA3B, and various groups have reported identifying deletions in this gene in different tumors. Using a high density of PCR amplifiable markers within FRA3B searching for deletions in the FRA3B region, we have analysed 21 tumor cell lines derived from renal cell, pancreatic, and ovarian carcinomas. We found a commonly deleted region in the renal cell and ovarian carcinoma cell lines located in the middle of an HPV16 viral integration site. Despite the presence of deletions in the FRA3B region in most of the cell lines, we did not detect alterations in FHIT exons in any of the cell lines examined. Thus, deletions of 3p14.2 in these carcinoma cell lines may simply reflect instability of the FRA3B region during tumor progression.
位于人类染色体3p14.2带的FRA3B是人类基因组中最活跃的常见脆性位点。该区域脆性的分子机制尚不清楚，但不像一些已克隆的罕见脆性位点那样涉及三核苷酸或微卫星重复序列的扩增。在许多不同的肿瘤中都观察到了FRA3B处的缺失和重排。最近鉴定出的假定肿瘤抑制基因FHIT跨越FRA3B，不同研究小组报告在不同肿瘤中发现了该基因的缺失。我们利用FRA3B内高密度的可PCR扩增标记物来寻找FRA3B区域的缺失，分析了21种来源于肾细胞癌、胰腺癌和卵巢癌的肿瘤细胞系。我们在肾细胞癌和卵巢癌细胞系中发现了一个常见的缺失区域，该区域位于HPV16病毒整合位点的中间。尽管大多数细胞系的FRA3B区域存在缺失，但在我们检测的任何细胞系中均未检测到FHIT外显子的改变。因此，这些癌细胞系中3p14.2的缺失可能仅仅反映了肿瘤进展过程中FRA3B区域的不稳定性。
