Integration of global SNP-based mapping and expression arrays reveals key regions, mechanisms, and genes important in the pathogenesis of multiple myeloma.

B.A. Walker, P.E. Leone, M.W. Jenner, C. Li, D. Gonzalez, D.C. Johnson, F.M. Ross, F.E. Davies, G.J. Morgan

Research output: Contribution to journalArticle

156 Citations (Scopus)

Abstract

Multiple myeloma is characterized by genomic alterations frequently involving gains and losses of chromosomes. Single nucleotide polymorphism (SNP)-based mapping arrays allow the identification of copy number changes at the sub-megabase level and the identification of loss of heterozygosity (LOH) due to monosomy and uniparental disomy (UPD). We have found that SNP-based mapping array data and fluorescence in situ hybridization (FISH) copy number data correlated well, making the technique robust as a tool to investigate myeloma genomics. The most frequently identified alterations are located at 1p, 1q, 6q, 8p, 13, and 16q. LOH is found in these large regions and also in smaller regions throughout the genome with a median size of 1 Mb. We have identified that UPD is prevalent in myeloma and occurs through a number of mechanisms including mitotic nondisjunction and mitotic recombination. For the first time in myeloma, integration of mapping and expression data has allowed us to reduce the complexity of standard gene expression data and identify candidate genes important in both the transition from normal to monoclonal gammopathy of unknown significance (MGUS) to myeloma and in different subgroups within myeloma. We have documented these genes, providing a focus for further studies to identify and characterize those that are key in the pathogenesis of myeloma.
Original languageEnglish
Pages (from-to)1733-1743
Number of pages11
JournalBlood
Volume108
Issue number5
DOIs
Publication statusPublished - 01 Sep 2006

Keywords

  • Bone Marrow
  • Chromosome Mapping
  • Gene Expression Regulation, Neoplastic
  • Genome, Human
  • Humans
  • Loss of Heterozygosity
  • Multiple Myeloma
  • Oligonucleotide Array Sequence Analysis
  • Polymorphism, Single Nucleotide
  • Uniparental Disomy

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