Molecular cytogenetic aberrations in CD30+ anaplastic large cell lymphoma cell lines
Molecular cytogenetic aberrations in CD30+ anaplastic large cell lymphoma cell lines
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DOI：
10.1016/s0165-4608(02)00589-7
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发表时间：
2002-10-15
影响因子：
--
通讯作者：
Nezelof, C
中科院分区：
文献类型：
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作者：
Gogusev, J;Telvi, L;Nezelof, C
儿童间变性大细胞淋巴瘤（ALCL）在涉及细胞谱系方面代表了一组异质性肿瘤。染色体5q35断点（bp）和NPM/ALK融合基因的表达是这些恶性肿瘤最显著的分子细胞遗传学特征。为了确定ALCL相关癌基因的新位置，将比较基因组杂交（CGH）应用于三个ALCL细胞系（SU-DHL-1， Karpas 299和DEL），显示5q35 bp并表达NPM/ALK转录物。比较了两名ALCL患儿的U937、HL-60细胞DNA和改变的淋巴结的CGH谱。在所有ALCL细胞系中，在多条染色体上观察到显著的DNA拷贝数增加和/或减少。在1q21similar toq44 （DEL）、7q12 （SU-DHL-1）和1q12similar toq22 （Karpas 299）区域检测到不同的扩增子。通过荧光原位杂交（FISH）分析，在80%以上的间期细胞核和中期扩散中证实了NPM/ALK融合基因。Northern blot分析显示，DEL和SU-DHL1细胞系扩增区tgf - β 2和c-MET候选基因表达增强。这些发现描述了ALCL衍生细胞系的染色体失衡与覆盖靶DNA序列的高水平扩增平行，这可能在ALCL发病机制中发挥作用。(C) 2002爱思唯尔科学有限公司版权所有。
Anaplastic large cell lymphomas (ALCL) in children represent a heterogeneous group of neoplasms with regard to the cell lineages involved. The chromosomal 5q35 breakpoint (bp) and the expression of the NPM/ALK fusion gene are the most remarkable molecular cytogenetic features of these malignancies. To identify new locations of ALCL-related oncogenes, comparative genomic hybridization (CGH) was applied to three ALCL cell lines (SU-DHL-1, Karpas 299, and DEL) exhibiting the 5q35 bp and expressing the NPM/ALK transcript. The CGH profiles were compared with those obtained with DNA from U937, HL-60 cells, and altered lymph nodes from two children with ALCL. Significant DNA copy number gains and/or losses were observed on several chromosomes in all ALCL cell lines. Distinct amplicons were detected on 1q21similar toq44 (DEL), 7q12 (SU-DHL-1), and 1q12similar toq22 (Karpas 299) regions. The NPM/ALK fusion gene was confirmed by fluorescence in situ hybridization (FISH) analysis in more than 80% of interphase nuclei and metaphase spreads. Enhanced expression of TGF-beta2 and c-MET candidate genes located at the amplified regions was revealed in DEL and SU-DHL1 cell lines by Northern blot analysis. These findings delineate chromosomal imbalances in ALCL-derived cell lines in parallel with high level of amplification covering target DNA sequences, which could play a role in ALCL pathogenesis. (C) 2002 Elsevier Science Inc. All rights reserved.