Ramirez Tzutzuy, Thoma Karen, Taja-Chayeb Lucia, Efferth Thomas, Herrera Luis A, Halatsch Marc-Eric, Gebhart Erich
Institute of Human Genetics, University of Erlangen-Nuremberg, D-91054 Erlangen, Germany.
Int J Oncol. 2003 Aug;23(2):453-60.
Eight cell lines newly established from glioblastoma multiforme were examined by comparative genomic hybridization for their patterns of genomic imbalance. The total number of DNA copy number alterations (CNAs) found in the eight cell lines varied between 15 and 24. This characterized the examined cell lines (or the tumors they were derived from) as distinctly progressed in karyotypic evolution. The most frequent CNAs were gains of the entire chromosome 6 or, at least, parts of it, and of 7p22, which were found in all eight cell lines. Other changes present in seven of the eight cell lines were gains of 3q26qter and the entire chromosome 7 and losses of segments on chromosome 4q (e.g., 4q34q35) and of the short arm of chromosome 10. Enh(3q21q25), dim(4q22q33) and dim(4qter), dim(13q22), enh(15q14), and enh(18q22q23) were found in six of the eight cell lines. Several other CNAs [e.g., dim(9p21)] were found in common in five or less of the eight lines. Using a hierarchical cluster analysis, the specific patterns of genomic imbalance allowed various groupings of the examined cell lines. Although a close relation could be confirmed among all examined lines on the basis of shared CNAs, two main groups could be roughly differentiated. Among those there were also more or less closely related subgroups. However, also alterations which were restricted to one single cell line each were found, e.g., dim(1q41qter), dim(2q22qter), enh(4p), dim(5p), dim(4p13pter), dim(8q21qter), enh(9p), dim(9q), dim(11p14pter), enh(12q15q23), enh(13q21), dim(14q21qter), dim(15q21qter), dim(19q), and enh(22q). The comparison of the obtained data on gains and losses of DNA copy numbers in specific chromosomal segments with the data on localization of genes possibly associated with the biology of glioblastoma multiforme additionally shows high conformity but also disparity of the examined cell lines among each other, as well as compared to primary glioblastoma multiforme. Eventually, each of the cell lines could be characterized by its specific pattern of genomic imbalance.
通过比较基因组杂交技术，对新建立的8种多形性胶质母细胞瘤细胞系的基因组失衡模式进行了检测。在这8种细胞系中发现的DNA拷贝数改变（CNA）总数在15至24之间。这表明所检测的细胞系（或其来源的肿瘤）在核型进化中已明显进展。最常见的CNA是整条染色体6或其至少部分区域以及7p22区域的增加，这在所有8种细胞系中均有发现。在8种细胞系中的7种中出现的其他变化包括3q26qter区域和整条染色体7的增加以及4号染色体上某些片段（如4q34q35）和10号染色体短臂的缺失。在8种细胞系中的6种中发现了增强子（3q21q25）、缺失区域（4q22q33）和缺失区域（4q末端）、缺失区域（13q22）、增强子（15q14）以及增强子（18q22q23）。在8种细胞系中，有几种其他的CNA（如缺失区域（9p21））在5种或更少的细胞系中共同出现。使用层次聚类分析，基因组失衡的特定模式允许对所检测的细胞系进行各种分组。尽管基于共享的CNA可以确认所有检测的细胞系之间存在密切关系，但大致可以区分出两个主要组。在这些组中也存在或多或少密切相关的亚组。然而，也发现了仅局限于单个细胞系的改变，例如缺失区域（1q41q末端）、缺失区域（2q22q末端）、增强子（4p）、缺失区域（5p）、缺失区域（4p13p末端）、缺失区域（8q21q末端）、增强子（9p）、缺失区域（9q）、缺失区域（11p14p末端）、增强子（12q15q23）、增强子（13q21）、缺失区域（14q21q末端）、缺失区域（15q21q末端）、缺失区域（19q）以及增强子（22q）。将在特定染色体片段中获得的DNA拷贝数增减数据与可能与多形性胶质母细胞瘤生物学相关的基因定位数据进行比较，结果还表明，所检测的细胞系彼此之间以及与原发性多形性胶质母细胞瘤相比，既有高度的一致性，也存在差异。最终，每种细胞系都可以通过其特定的基因组失衡模式来表征。
