Elsevier

Genomics

Volume 71, Issue 2, 15 January 2001, Pages 214-221
Genomics

Regular Article
The MEIS1 Oncogene Is Highly Expressed in Neuroblastoma and Amplified in Cell Line IMR32

https://doi.org/10.1006/geno.2000.6408Get rights and content

Abstract

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.

References (38)

  • J. Berthelsen et al.

    The subcellular localization of PBX1 and EXD proteins depends on nuclear import and export signals and is modulated by association with PREP1 and HTH

    Genes Dev.

    (1999)
  • J. Borrow et al.

    The t(7;11)(p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP98 and class I homeoprotein HOXA9

    Nat. Genet.

    (1996)
  • C. Brinkschmidt et al.

    Comparative genomic hybridization (CGH) analysis of neuroblastomas—An important methodological approach in paediatric tumour pathology

    J. Pathol.

    (1997)
  • G.M. Brodeur et al.

    Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage

    Science

    (1984)
  • G.M. Brodeur et al.

    Chromosomal aberrations in human neuroblastomas

    Cancer

    (1977)
  • N.C. Cheng et al.

    Deletion mapping in neuroblastoma cell lines suggests two distinct tumor suppressor genes in the 1p35–36 region, only one of which is associated with N-myc amplification

    Oncogene

    (1995)
  • P. Deloukas et al.

    A physical map of 30,000 human genes

    Science

    (1998)
  • A.E. Evans et al.

    A proposed staging for children with neuroblastoma. Children's cancer study group A

    Cancer

    (1971)
  • Cited by (0)

    Sequence data from this article have been deposited with the EMBL/GenBank Data Libraries under Accession No. AZ081511.

    1

    To whom correspondence should be addressed. Telephone: 0031-20-5665243. Fax: 0031-20-6918626. E-mail: [email protected].

    View full text