Richter J, Jiang F, Görög J P, Sartorius G, Egenter C, Gasser T C, Moch H, Mihatsch M J, Sauter G
Institute of Pathology, University of Basel, Switzerland.
Cancer Res. 1997 Jul 15;57(14):2860-4.
Little is known about the genetic changes underlying invasive tumor growth in bladder cancer. Because alterations that are linked to invasive tumor growth may be detectable in minimally invasive (stage pT1) but not in noninvasive (stage pTa) tumors, we searched for genetic differences between 28 pTa and 28 papillary pT1 bladder tumors by comparative genomic hybridization. Losses of 9q (54%), 9p (39%), and Y (28%) and gains of 1q (14%) were most prevalent in pTa tumors. These changes may play a role in the initiation of noninvasive papillary bladder cancer. The total number of aberrations was higher in pT1 tumors (6.5 +/- 5.4) than in pTa tumors (2.3 +/- 2.1; P = 0.0003), suggesting an increased genetic instability at stage pT1. Specific alterations, which were significantly more frequent in pT1 than in pTa tumors (P < or = 0.05), included deletions at 2q (36% of pT1 tumors), 8p (32%), and 11p (21%) and gains at 1q (54%), 8q (32%), 3p, 3q, 5p, 6p, and 10p (18% each). These loci are candidates for carrying genes involved in invasive tumor growth in bladder cancer. High-level amplifications at 1q22-24, 3p24-25, 6p22, 8p12, 8q21-22, 10p12.1-14, 11q13, 12q15-21, 13q31-33, Xp11-13, and Xq21-22.2 may pinpoint the location of oncogenes with relevance for bladder cancer.
关于膀胱癌侵袭性肿瘤生长背后的基因变化，人们了解甚少。由于与侵袭性肿瘤生长相关的改变可能在微侵袭性（pT1期）肿瘤中可检测到，但在非侵袭性（pTa期）肿瘤中无法检测到，因此我们通过比较基因组杂交技术寻找28例pTa期和28例乳头状pT1期膀胱肿瘤之间的基因差异。9号染色体长臂（9q，54%）、9号染色体短臂（9p，39%）和Y染色体（28%）的缺失以及1号染色体长臂（1q，14%）的增加在pTa期肿瘤中最为常见。这些变化可能在非侵袭性乳头状膀胱癌的起始过程中发挥作用。pT1期肿瘤的畸变总数（6.5±5.4）高于pTa期肿瘤（2.3±2.1；P = 0.0003），这表明pT1期的基因不稳定性增加。在pT1期肿瘤中比在pTa期肿瘤中显著更频繁出现的特定改变（P≤0.05）包括2号染色体短臂（2q，36%的pT1期肿瘤）、8号染色体短臂（8p，32%）和11号染色体短臂（11p，21%）的缺失以及1号染色体长臂（1q，54%）、8号染色体长臂（8q，32%）、3号染色体短臂、3号染色体长臂、5号染色体短臂、6号染色体短臂和10号染色体短臂（均为18%）的增加。这些位点是携带参与膀胱癌侵袭性肿瘤生长相关基因的候选位点。1q22 - 24、3p24 - 25、6p22、8p12、8q21 - 22、10p12.1 - 14、11q13、12q15 - 21、13q31 - 33、Xp11 - 13和Xq21 - 22.2处的高水平扩增可能确定了与膀胱癌相关的癌基因位置。
