Kerr J, Leary J A, Hurst T, Shih Y C, Antalis T M, Friedlander M, Crawford E, Khoo S K, Ward B, Chenevix-Trench G
Queensland Cancer Fund Research Unit, The Queensland Institute of Medical Research, Brisbane, Australia.
Oncogene. 1996 Oct 17;13(8):1815-8.
The presence of a tumour suppressor gene on chromosome 7q is indicated by cytogenetic, loss of heterozygosity (LOH) and chromosome transfer studies. One candidate gene in this region is Plasminogen Activator Inhibitor-1 (PAI-1). The PAI-1 gene product is involved in proteolysis and may therefore influence tumour spread and invasion. We have analysed a series of 139 ovarian epithelial tumours at four loci in the region 7q21-q31 which includes the PAI-1 gene. The highest rates of loss were found in malignant tumours (FIGO stages I-IV) at markers D7S471 (38%, 20/52 informative cases) and D7S522 (34%, 15/44). No loss was seen in benign tumours and only one out of 27 (4%) informative LMP tumours demonstrated LOH. The smallest region of overlap (SRO) lies between D7S471 and PAI-1. We also identified a rearrangement in one tumour in the PAI-1 gene, suggesting that this may be the inactivated gene in this region. In addition LOH at the more distal marker, D7S522, which lies outside the SRO, shows significant association with stage (P=0.0343) and with LOH on chromosome 13 (P=0.0024). This is in contrast to all other markers examined. These data suggest the presence of two critical regions on 7q which may be important in subsets of epithelial ovarian tumours.
细胞遗传学、杂合性缺失（LOH）及染色体转移研究表明7号染色体长臂（7q）上存在一个肿瘤抑制基因。该区域的一个候选基因是纤溶酶原激活物抑制剂-1（PAI-1）。PAI-1基因产物参与蛋白水解，因此可能影响肿瘤的扩散和侵袭。我们分析了139例卵巢上皮性肿瘤，检测了7q21-q31区域（包括PAI-1基因）的四个位点。在恶性肿瘤（国际妇产科联盟（FIGO）分期I-IV期）中，标记物D7S471（38%，20/52例信息性病例）和D7S522（34%，15/44）的缺失率最高。良性肿瘤未发现缺失，27例信息性交界性肿瘤中仅1例（4%）显示杂合性缺失。最小重叠区域（SRO）位于D7S471和PAI-1之间。我们还在一个肿瘤中发现了PAI-1基因重排，提示该基因可能是该区域的失活基因。此外，位于SRO之外更远端的标记物D7S522处的杂合性缺失与分期（P=0.0343）及13号染色体上的杂合性缺失（P=0.0024）显著相关。这与所检测的所有其他标记物情况相反。这些数据提示7q上存在两个关键区域，它们在上皮性卵巢肿瘤的某些亚组中可能很重要。
