Gibas Z, Prout G R, Connolly J G, Pontes J E, Sandberg A A
Cancer Res. 1984 Mar;44(3):1257-64.
Nine cases of transitional cell carcinoma (eight from the urinary bladder and one from the ureter; six noninvasive and three invasive) were subjected to detailed cytogenetic analysis with a G-banding method. The synchronization of primary cultures with methotrexate for high-resolution banding was performed in five cases. In the remaining four cases, the chromosomes were obtained from short-term cultures after prolonged (16 hr) exposure to Colcemid. Two cases were near-tetraploid, one was hypotriploid, and six were near-diploid (three hyperdiploid and three hypodiploid). All but one case showed various structural abnormalities in the karyotype. The chromosomal changes ranged from the presence of only two abnormal chromosomes (markers) to complex karyotypes with as many as 15 markers. In most tumors, the origin of the marker chromosomes could be readily deciphered. The nonrandom chromosomal aberrations included: (a) an isochrosome of the short arm of chromosome 5 (three cases); (b) monosomy of chromosome 9 found in four cases (this was the sole abnormality in one case); (c) involvement of chromosome 8 as an isochromosome of the long arm (two cases) or loss of the short arm due to deletion (one case) or translocation (one case); and (d) interstitial deletion of chromosome 13 (three cases). Our results indicate that the formation of i(5p) and monosomy 9 may be the primary karyotypic changes in two subgroups of transitional cell carcinoma. Involvement of chromosomes 8 and 13, on the other hand, seems to be a result of secondary karyotypic evolution. Two invasive tumors showed the presence of secondary clones, with additional structural chromosome aberrations superimposed on those already existing in the main cell population. In both cases, the additional aberrations involved the short arm of chromosome 11, resulting in loss of genetic material from the short arm. The short arm of chromosome 11, is the putative site of an oncogene which has been isolated from human bladder carcinoma cell lines. Deletion of the 11p was also seen in one case of noninvasive transitional cell carcinoma localized in the ureter; the material from 11p was probably translocated to chromosome 13. These findings suggest that the loss of genetic material from the short arm of chromosome 11 is a secondary event in the karyotypic evolution of transitional cell carcinoma, probably related to the invasive behavior of the tumor.
9例移行细胞癌（8例来自膀胱，1例来自输尿管；6例非侵袭性，3例侵袭性）采用G显带法进行了详细的细胞遗传学分析。5例原代培养物用甲氨蝶呤同步化以进行高分辨显带。其余4例，染色体是从经秋水仙酰胺长时间（16小时）处理后的短期培养物中获得的。2例为近四倍体，1例为亚三倍体，6例为近二倍体（3例超二倍体和3例亚二倍体）。除1例之外，所有病例的核型均显示出各种结构异常。染色体改变范围从仅存在两条异常染色体（标记染色体）到具有多达15条标记染色体的复杂核型。在大多数肿瘤中，标记染色体的来源很容易识别。非随机染色体畸变包括：（a）5号染色体短臂的等臂染色体（3例）；（b）4例中发现9号染色体单体（其中1例这是唯一的异常）；（c）8号染色体作为长臂等臂染色体受累（2例）或因缺失（1例）或易位（1例）导致短臂丢失；以及（d）13号染色体的中间缺失（3例）。我们的结果表明，i(5p)的形成和9号染色体单体可能是移行细胞癌两个亚组中的主要核型变化。另一方面，8号和13号染色体受累似乎是核型继发性进化的结果。2例侵袭性肿瘤显示存在次要克隆，其具有叠加在主要细胞群体中已存在的结构染色体畸变之上的额外结构染色体畸变。在这两个病例中，额外的畸变均累及11号染色体短臂，导致短臂遗传物质丢失。11号染色体短臂是已从人膀胱癌细胞系中分离出的一个癌基因的假定位点。在1例位于输尿管的非侵袭性移行细胞癌中也观察到11p缺失；11p的物质可能易位至13号染色体。这些发现表明，11号染色体短臂遗传物质的丢失是移行细胞癌核型进化中的一个次要事件，可能与肿瘤的侵袭行为有关。
