Hukku B, Rhim J S
Children's Hospital of Michigan, Department of Pediatrics, Detroit 48201.
Cancer Genet Cytogenet. 1993 Jul 1;68(1):22-31. doi: 10.1016/0165-4608(93)90069-x.
Rhim et al. were first to show that superinfection of Ad12-SV40-infected immortalized human epidermal cells with an RNA tumor virus containing a ras oncogene, such as Ki-MSV, or their treatment with chemical carcinogens, leads to the ability of cells to both grow in anchorage-independent fashion and to form tumors in athymic nude mice. We describe details of the chromosome changes observed during the transformation. The culture was monitored through 40 passages after Ad12-SV40 infection. Chromosomes 9 and 11 showed random monosomy during the initial stages, but by passage 10 clonal evolution of the cell line was well established. Observed chromosome monosomy/trisomy coupled with chromosome rearrangements (identified as chromosomes A through F) were monosomy 13, loss of p arms of 8 and 10, partial loss of 5 (del(5)(q13) and of the q arm of 18(del(18)(q12)), and extra copies of 11q, 20 and 21. During its progression to tumorigenicity, a derived chromosome E containing a segment of 5q, also appeared to play a major role. The cells remained immortalized as long as the 5q segment was present in some of the cell population as derived chromosomes E or F. Derivative chromosome E showed noteworthy changes during the progression to tumorigenicity, in both viral and chemical transformations. There was loss of heterozygosity of 5q due to an exchange of 5q with chromosomes E or F. In Ki-MSV- and 4NQO-transformed cells, presence of an altered chromosome E (identified as E1) was observed. In MNNG-treated cells, there was a selection of population of cells with further alteration in chromosome E (identified as E3). Besides alterations in chromosome E, additional chromosome changes leading to gene activation and amplification indicating a multistep progression to tumorigenicity were observed. The cytogenetic data reiterate the ever-increasing need for molecular analysis of nonrandom karyotype changes.
里姆等人首先表明，用含有ras癌基因的RNA肿瘤病毒（如Ki-MSV）对Ad12-SV40感染的永生化人表皮细胞进行超感染，或用化学致癌物处理这些细胞，会导致细胞能够以不依赖贴壁的方式生长，并在无胸腺裸鼠中形成肿瘤。我们描述了转化过程中观察到的染色体变化细节。在Ad12-SV40感染后，对该培养物进行了40代监测。在初始阶段，9号和11号染色体出现随机单体性，但到第10代时，细胞系的克隆进化已充分确立。观察到的染色体单体性/三体性以及染色体重排（鉴定为A至F号染色体）包括13号染色体单体性、8号和10号染色体短臂缺失、5号染色体部分缺失（del(5)(q13)）和18号染色体长臂缺失（del(18)(q12)），以及11q、20号和21号染色体的额外拷贝。在其向致瘤性进展过程中，一条含有5q片段的衍生染色体E似乎也起了主要作用。只要5q片段以衍生染色体E或F的形式存在于部分细胞群体中，细胞就保持永生化。衍生染色体E在向致瘤性进展过程中，在病毒和化学转化中均显示出值得注意的变化。由于5q与染色体E或F的交换，5q出现杂合性缺失。在Ki-MSV和4NQO转化的细胞中，观察到一条改变的染色体E（鉴定为E1）。在MNNG处理的细胞中，选择了染色体E进一步改变的细胞群体（鉴定为E3）。除了染色体E的改变外，还观察到导致基因激活和扩增的其他染色体变化，表明向致瘤性的多步骤进展。细胞遗传学数据再次强调了对非随机核型变化进行分子分析的迫切需求。
