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.
Copyright 2001 Academic Press.