title: The progression from MGUS to smoldering myeloma and eventually to multiple myeloma involves a clonal expansion of genetically abnormal plasma cells.
abstract: OBJECTIVE
  Genetic aberrations detected in multiple myeloma (MM) have also been reported in the premalignant conditions monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM). Our aim was to investigate in depth the level of clonal heterogeneity of recurrent genetic abnormalities in these conditions.
  
  
  METHODS
  Immunoglobulin heavy chain (IGH) translocations, 13q14 and 17p13 deletions, and 1q21 gains using FISH were evaluated in 90 MGUS, 102 high-risk SMM, and 373 MM. To this end, we not only purified plasma cells (PC) for the FISH analysis (purity > 90%), but subsequently, we examined the correlation between the proportion of PC with cytogenetic changes and the number of clonal PC present in the same sample, as measured by multiparametric flow cytometry.
  
  
  RESULTS
  We observed a significant difference between the proportion of clonal PC with specific genetic abnormalities in MGUS compared with SMM and in SMM compared with MM. Thus, the median proportion of PC with IGH translocations globally considered, t(11;14) and 13q deletions was significantly lower in MGUS than in SMM, and in SMM than in MM [IGH translocations: 34% vs. 57% vs. 76%; t(11;14): 38% vs. 61% vs. 81%; and 13q deletion: 37% vs. 61% vs. 74% in MGUS, SMM, and MM, respectively]. For t(4;14), the difference was significant in the comparison between MGUS/SMM and MM and for 1q between MGUS and SMM/MM.
  
  
  CONCLUSIONS
  This study demonstrates that the progression from MGUS to SMM, and eventually to MM, involves a clonal expansion of genetically abnormal PC.
authors.affiliation: Servicio de Hematología, Hospital Universitario, Universidad de Salamanca, Salamanca, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: López-Corral
authors.forename: Norma C
authors.initials: NC
authors.lastname: Gutiérrez
authors.forename: Maria Belén
authors.initials: MB
authors.lastname: Vidriales
authors.forename: Maria Victoria
authors.initials: MV
authors.lastname: Mateos
authors.forename: Ana
authors.initials: A
authors.lastname: Rasillo
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Sanz
authors.forename: Bruno
authors.initials: B
authors.lastname: Paiva
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
mesh_terms: D049109:Cell Proliferation; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D018450:Disease Progression; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D009101:Multiple Myeloma / Q000235:genetics / Q000473:pathology*; D010265:Paraproteinemias / Q000235:genetics / Q000473:pathology*; D010950:Plasma Cells / Q000473:pathology*; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology*; D017384:Sequence Deletion; D014178:Translocation, Genetic
chemical_list: D007143:Immunoglobulin Heavy Chains