Insights into the multistep transformation of MGUS to myeloma using microarray expression analysis.

F.E. Davies, A.M. Dring, C. Li, A.C. Rawstron, M.A. Shammas, S.M. O'Connor, J.A. Fenton, T. Hideshima, D. Chauhan, I.T. Tai, E. Robinson, D. Auclair, K. Rees, D. Gonzalez, A.J. Ashcroft, R. Dasgupta, C. Mitsiades, N. Mitsiades, L.B. Chen, W.H. WongN.C. Munshi, G.J. Morgan, K.C. Anderson

Research output: Contribution to journalArticle

194 Citations (Scopus)

Abstract

To define specific pathways important in the multistep transformation process of normal plasma cells (PCs) to monoclonal gammopathy of uncertain significance (MGUS) and multiple myeloma (MM), we have applied microarray analysis to PCs from 5 healthy donors (N), 7 patients with MGUS, and 24 patients with newly diagnosed MM. Unsupervised hierarchical clustering using 125 genes with a large variation across all samples defined 2 groups: N and MGUS/MM. Supervised analysis identified 263 genes differentially expressed between N and MGUS and 380 genes differentially expressed between N and MM, 197 of which were also differentially regulated between N and MGUS. Only 74 genes were differentially expressed between MGUS and MM samples, indicating that the differences between MGUS and MM are smaller than those between N and MM or N and MGUS. Differentially expressed genes included oncogenes/tumor-suppressor genes (LAF4, RB1, and disabled homolog 2), cell-signaling genes (RAS family members, B-cell signaling and NF-kappaB genes), DNA-binding and transcription-factor genes (XBP1, zinc finger proteins, forkhead box, and ring finger proteins), and developmental genes (WNT and SHH pathways). Understanding the molecular pathogenesis of MM by gene expression profiling has demonstrated sequential genetic changes from N to malignant PCs and highlighted important pathways involved in the transformation of MGUS to MM.
Original languageEnglish
Pages (from-to)4504-4511
Number of pages8
JournalBlood
Volume102
Issue number13
DOIs
Publication statusPublished - 15 Dec 2003

Keywords

  • Cell Transformation, Neoplastic
  • DNA-Binding Proteins
  • Disease Progression
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Multiple Myeloma
  • Neoplasm Proteins
  • Oligonucleotide Array Sequence Analysis
  • Oncogene Proteins
  • Paraproteinemias
  • Precancerous Conditions
  • Subtraction Technique
  • Transcription Factors

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  • Cite this

    Davies, F. E., Dring, A. M., Li, C., Rawstron, A. C., Shammas, M. A., O'Connor, S. M., Fenton, J. A., Hideshima, T., Chauhan, D., Tai, I. T., Robinson, E., Auclair, D., Rees, K., Gonzalez, D., Ashcroft, A. J., Dasgupta, R., Mitsiades, C., Mitsiades, N., Chen, L. B., ... Anderson, K. C. (2003). Insights into the multistep transformation of MGUS to myeloma using microarray expression analysis. Blood, 102(13), 4504-4511. https://doi.org/10.1182/blood-2003-01-0016