title: Insights into the multistep transformation of MGUS to myeloma using microarray expression analysis.
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.
authors.affiliation: Academic Unit of Haematology and Oncology, Algernon Firth Bldg, School of Medicine, University of Leeds, Leeds, United Kingdom. faith@egu.leeds.ac.uk
authors.forename: Faith E
authors.initials: FE
authors.lastname: Davies
authors.forename: Ann M
authors.initials: AM
authors.lastname: Dring
authors.forename: Cheng
authors.initials: C
authors.lastname: Li
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Rawstron
authors.forename: Masood A
authors.initials: MA
authors.lastname: Shammas
authors.forename: Sheila M
authors.initials: SM
authors.lastname: O'Connor
authors.forename: James A L
authors.initials: JA
authors.lastname: Fenton
authors.forename: Teru
authors.initials: T
authors.lastname: Hideshima
authors.forename: Dharminder
authors.initials: D
authors.lastname: Chauhan
authors.forename: Isabella T
authors.initials: IT
authors.lastname: Tai
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Robinson
authors.forename: Daniel
authors.initials: D
authors.lastname: Auclair
authors.forename: Karen
authors.initials: K
authors.lastname: Rees
authors.forename: David
authors.initials: D
authors.lastname: Gonzalez
authors.forename: A John
authors.initials: AJ
authors.lastname: Ashcroft
authors.forename: Ranjit
authors.initials: R
authors.lastname: Dasgupta
authors.forename: Constantine
authors.initials: C
authors.lastname: Mitsiades
authors.forename: Nicholas
authors.initials: N
authors.lastname: Mitsiades
authors.forename: Lan B
authors.initials: LB
authors.lastname: Chen
authors.forename: Wing H
authors.initials: WH
authors.lastname: Wong
authors.forename: Nikhil C
authors.initials: NC
authors.lastname: Munshi
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Morgan
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D018450:Disease Progression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics / Q000473:pathology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D010265:Paraproteinemias / Q000235:genetics / Q000473:pathology*; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology*; D013382:Subtraction Technique; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D014157:Transcription Factors