The MEIS1 oncogene is highly expressed in neuroblastoma and amplified in cell line IMR32

Neuroblastoma is an embryonal tumor originating from neural crest-derived c ells. Here we present the serendipitous cloning of amplified sequences of c hromosome 2p15 in neuroblastoma cell line IMR32. The amplified region was a nalyzed for oncogene activation using a SAGE (serial analysis of gene expre ssion) library of IMR32. SAGE permits a quantitative analysis of all transc ripts of a tissue or cell line. The expression of genes and ESTs mapping wi thin 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 th e MEIS1 oncogene, whereas other SAGE libraries showed little or no IMEIS1 e xpression. MEIS1 turned out to be highly amplified and overexpressed in IMR 32. 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 c omplex with the HOXA9 and PBX proteins that are implicated in human leukemi a. MEIS1 is a target of retroviral insertion in murine leukemia. This is th e first report of a MEIS1 amplification and high expression levels in human cancer and the first time that identification of a candidate target of amp lification is facilitated by high-throughput mRNA expression profiling. (C) 2001 Academic Press.