title: Cytogenetic profiles in multiple myeloma and monoclonal gammopathy of undetermined significance: a study in highly purified aberrant plasma cells.
abstract: Cytogenetic studies in clonal plasma cell disorders have mainly been done in whole bone marrow or CD138(+) microbead-enriched plasma cells and suggest that recurrent immunoglobulin heavy chain translocations - e.g. t(4;14) -are primary oncogenetic events. The aim of this study was to determine cytogenetic patterns of highly purified aberrant plasma cells (median purity ≥ 98%) in different clonal plasma cell disorders. We analyzed aberrant plasma cells from 208 patients with multiple myeloma (n=148) and monoclonal gammopathy of undetermined significance (n=60) for the presence of del(13q14), del(17p13) and t(14q32) using multicolor interphase fluorescence in situ hybridization. Additionally, immunoglobulin heavy chain gene arrangements were analyzed and complementarity determining region 3 was sequenced in a subset of patients and combined multicolor interphase fluorescence in situ hybridization/immunofluorescent protein staining analyses were performed in selected cases to confirm clonality and cytogenetic findings. At diagnosis, 96% of cases with multiple myeloma versus 77% of monoclonal gammopathy of undetermined significance cases showed at least one cytogenetic alteration and/or hyperdiploidy. The cytogenetic heterogeneity of individual cases reflected coexistence of cytogenetically-defined aberrant plasma cell clones, and led to the assumption that karyotypic alterations were acquired stepwise. Cases of multiple myeloma and monoclonal gammopathy of undetermined significance frequently showed different but related cytogenetic profiles when other cytogenetic alterations such as deletions/gains of the immunoglobulin heavy chain or the fibroblast growth factor receptor 3 were additionally considered. Interestingly, in 24% of multiple myeloma versus 62% of monoclonal gammopathy of undetermined significance patients with an immunoglobulin heavy chain translocation, aberrant plasma cells with and without t(14q32) coexisted in the same patient. Our data suggest that recurrent immunoglobulin heavy chain translocations might be absent in the primordial plasma cell clone in a significant proportion of patients with clonal plasma cell disorders carrying these cytogenetic alterations.
authors.affiliation: Department of Medicine and Service of Cytometry, IBSAL and Centro de Investigación del Cáncer (IBMCC USAL-CSIC), University Hospital of Salamanca and University of Salamanca, Salamanca, Spain.
authors.forename: Martin
authors.initials: M
authors.lastname: Schmidt-Hieber
authors.forename: María Laura
authors.initials: ML
authors.lastname: Gutiérrez
authors.forename: Martin
authors.initials: M
authors.lastname: Pérez-Andrés
authors.forename: Bruno
authors.initials: B
authors.lastname: Paiva
authors.forename: Ana
authors.initials: A
authors.lastname: Rasillo
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Tabernero
authors.forename: José Maria
authors.initials: JM
authors.lastname: Sayagués
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez
authors.forename: Paloma
authors.initials: P
authors.lastname: Bárcena
authors.forename: María Luz
authors.initials: ML
authors.lastname: Sanchez
authors.forename: Norma C
authors.initials: NC
authors.lastname: Gutiérrez
authors.forename: Jesus F
authors.initials: JF
authors.lastname: San Miguel
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
mesh_terms: D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D016130:Immunophenotyping; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000235:genetics*; D009101:Multiple Myeloma / Q000235:genetics*; D010950:Plasma Cells / Q000378:metabolism* / Q000473:pathology*; D011003:Ploidies; D014178:Translocation, Genetic
chemical_list: D007143:Immunoglobulin Heavy Chains