Spieker N, van Sluis P, Beitsma M, Boon K, van Schaik B D, van Kampen A H, Caron H, Versteeg R
Department of Human Genetics, University of Amsterdam, Amsterdam, 1100DE, The Netherlands.
Genomics. 2001 Jan 15;71(2):214-21. doi: 10.1006/geno.2000.6408.
Neuroblastoma is an embryonal tumor originating from neural crest-derived cells. Here we present the serendipitous cloning of amplified sequences of chromosome 2p15 in neuroblastoma cell line IMR32. The amplified region was analyzed for oncogene activation using a SAGE (serial analysis of gene expression) library of IMR32. SAGE permits a quantitative analysis of all transcripts of a tissue or cell line. The expression of genes and ESTs mapping within a 30-cR region covering the amplicon was compared to 4 additional SAGE libraries of neuroblastomas and 12 SAGE libraries of other tissues in the CGAP databases. The IMR32 SAGE database revealed increased expression of the MEIS1 oncogene, whereas other SAGE libraries showed little or no MEIS1 expression. MEIS1 turned out to be highly amplified and overexpressed in IMR32. Analysis of 24 neuroblastoma cell lines and 22 tumors showed high-level expression in about 25% of the cases. The MEIS1 homeobox protein forms a complex with the HOXA9 and PBX proteins that are implicated in human leukemia. MEIS1 is a target of retroviral insertion in murine leukemia. This is the first report of a MEIS1 amplification and high expression levels in human cancer and the first time that identification of a candidate target of amplification is facilitated by high-throughput mRNA expression profiling.
神经母细胞瘤是一种起源于神经嵴衍生细胞的胚胎性肿瘤。在此，我们展示了在神经母细胞瘤细胞系IMR32中偶然克隆出的2号染色体p15区域的扩增序列。利用IMR32的基因表达序列分析（SAGE）文库对扩增区域进行癌基因激活分析。SAGE可对组织或细胞系的所有转录本进行定量分析。将覆盖扩增子的30厘摩区域内定位的基因和EST的表达与CGAP数据库中另外4个神经母细胞瘤SAGE文库及12个其他组织的SAGE文库进行比较。IMR32 SAGE数据库显示MEIS1癌基因表达增加，而其他SAGE文库显示MEIS1表达很少或无表达。结果表明MEIS1在IMR32中高度扩增且过表达。对24个神经母细胞瘤细胞系和22个肿瘤的分析显示，约25%的病例中存在高水平表达。MEIS1同源框蛋白与参与人类白血病的HOXA9和PBX蛋白形成复合物。MEIS1是鼠白血病中逆转录病毒插入的靶点。这是关于MEIS1在人类癌症中扩增及高表达水平的首次报道，也是首次通过高通量mRNA表达谱分析促进扩增候选靶点的鉴定。
