Sauter G, Moch H, Carroll P, Kerschmann R, Mihatsch M J, Waldman F M
Institute of Pathology, University of Basel, Switzerland.
Int J Cancer. 1995 Apr 21;64(2):99-103. doi: 10.1002/ijc.2910640205.
A loss of chromosome-9 material is one of the most frequent genomic aberrations known in bladder cancer. In order to better understand the role of chromosome-9 losses in bladder cancer, 125 formalin-fixed and 37 unfixed bladder tumors were examined using fluorescence in situ hybridization (FISH). A repetitive probe for a pericentromeric region on 9q12 (pHUR98) was applied for chromosome-9 copy-number enumeration. Under-representation of chromosome 9 was found in 74 of 162 cases. There was no association between loss of chromosome 9 and increased grade or stage, papillary growth pattern, p53 protein expression, or tumor-cell proliferation (Ki-67). These data show that chromosome-9 loss is an early event in bladder-cancer development, occurring independently of p53 alterations. In order to determine the prevalence of large sub-regional chromosome-9 deletions, dual hybridizations with pHUR98 and cosmid probes for 9q34, 9q22, and 9p21 were performed. Partial deletion was detected in only 1 of 36 cases for 9q34 and in 1 of 24 cases for 9p21. Surprisingly, amplification of the interferon alpha locus on 9p21 was seen in 1 of 24 tumors. The finding of 9p amplification may indicate the site of an oncogene relevant for bladder cancer.
9号染色体物质缺失是膀胱癌中已知的最常见基因组畸变之一。为了更好地理解9号染色体缺失在膀胱癌中的作用，我们使用荧光原位杂交（FISH）技术检测了125例福尔马林固定和37例未固定的膀胱肿瘤。应用针对9q12上着丝粒周围区域的重复探针（pHUR98）对9号染色体进行拷贝数计数。在162例病例中，有74例发现9号染色体呈现低拷贝数。9号染色体缺失与肿瘤分级或分期增加、乳头状生长模式、p53蛋白表达或肿瘤细胞增殖（Ki-67）之间均无关联。这些数据表明，9号染色体缺失是膀胱癌发生发展过程中的早期事件，其发生独立于p53改变。为了确定9号染色体大片段亚区域缺失的发生率，我们使用pHUR98和针对9q34、9q22及9p21的黏粒探针进行了双重杂交。在36例检测9q3�的病例中仅1例检测到部分缺失，在24例检测9p21的病例中也仅1例检测到部分缺失。令人惊讶的是，在24例肿瘤中有1例发现9p21上的干扰素α基因座发生扩增。9p扩增的发现可能提示了一个与膀胱癌相关的癌基因位点。
