Johansson B, Mertens F, Mitelman F
Department of Clinical Genetics, University Hospital, Lund, Sweden.
Genes Chromosomes Cancer. 1996 Jul;16(3):155-63. doi: 10.1002/(SICI)1098-2264(199607)16:3<155::AID-GCC1>3.0.CO;2-Y.
Two quite distinct neoplasia-associated karyotypic patterns are emerging. One is characterized by simple and disease-specific abnormalities, and the other is characterized by multiple and nonspecific aberrations. The former pattern is typical of most leukemias and lymphomas and of some mesenchymal tumors, but it is rare in epithelial neoplasms. The latter pattern is found in most epithelial tumor types, in several mesenchymal neoplasms, but in only a few hematologic malignancies. Primary chromosome aberrations, which are believed to be essential in establishing the neoplasm, and secondary changes, which are considered to be important in tumor progression, may be distinguished in the tumors characterized by simple and disease-specific abnormalities. Here, we propose that these aberrations are genetically and hence, most likely, functionally distinct. Primary abnormalities lead to specific gene rearrangements, whereas secondary chromosomal changes result in large-scale genomic imbalances. According to this hypothesis, there are no unbalanced primary aberrations, only secondary imbalances masquerading as primary. This proposition has a number of conceptual ramifications. First, the genetic mechanisms underlying tumor initiation and progression would seem to be totally different. Second, the elucidation of the molecular consequences of the secondary aberrations will be an arduous task, even if one were to adhere to the view that cytogenetically identified genomic imbalances may be reduced to simple gains or losses of single oncogenes or tumor suppressor genes. Third, the cytogenetic diagnosis of neoplasms will have to take into account that an unbalanced "primary" abnormality is secondary to a submicroscopic, truly primary change of major diagnostic and prognostic importance.
两种截然不同的与肿瘤形成相关的核型模式正在显现。一种以简单且疾病特异性的异常为特征，另一种则以多种非特异性畸变 为特征。前一种模式在大多数白血病、淋巴瘤以及一些间叶组织肿瘤中很典型，但在上皮性肿瘤中很少见。后一种模式在大多数上皮性肿瘤类型、几种间叶组织肿瘤中存在，但仅在少数血液系统恶性肿瘤中出现。在以简单且疾病特异性异常为特征的肿瘤中，可以区分出被认为对肿瘤形成至关重要的原发性染色体畸变和被认为对肿瘤进展很重要的继发性变化。在此，我们提出这些畸变在遗传上是不同的，因此很可能在功能上也是不同的。原发性异常导致特定的基因重排，而继发性染色体变化导致大规模的基因组失衡。根据这一假设，不存在不平衡的原发性畸变，只有伪装成原发性的继发性失衡。这一观点有许多概念上的影响。首先，肿瘤起始和进展的遗传机制似乎完全不同。其次，阐明继发性畸变的分子后果将是一项艰巨的任务，即使有人坚持认为细胞遗传学鉴定的基因组失衡可能简化为单个癌基因或肿瘤抑制基因的简单增减。第三，肿瘤的细胞遗传学诊断必须考虑到，一个不平衡的“原发性”异常是继发于一个具有主要诊断和预后重要性的亚微观、真正的原发性变化。
