title: NPM1 is overexpressed in hyperdiploid multiple myeloma due to a gain of chromosome 5 but is not delocalized to the cytoplasm.
abstract: Multiple myeloma (MM) is proposed to consist of two main pathogenetic groups. Although hyperdiploid MM (HD) is characterized by multiple trisomies of odd chromosomes, in nonhyperdiploid MM (NHD), one of the recurrent primary immunoglobulin heavy chain (IGH) translocations and deletion of chromosome 13 can frequently be found. In this study, we analyzed gene-expression profiles of patients with previously untreated MM. Fifty-four genes were significantly differentially expressed between the two groups. NPM1 was upregulated in HD. The differential expression of 25 genes, including NPM1 and 13 ribosomal protein genes, was validated using a published gene expression data set. The overexpression of NPM1 in HD was further confirmed by quantitative real-time PCR and Western blotting. NPM1 was significantly overexpressed in HD as the result of a gain of chromosome 5. Insertions into exon 12 of NPM1 were not detected. NPM1 was localized to the nucleoli of MM cells. Furthermore, HD was associated with an overexpression of ribosomal protein genes, independent of their localization on the trisomic or other chromosomes. Our results indicate that the gain of chromosome 5 might play an important role in the pathogenesis of HD.
authors.affiliation: Medizinische Klinik V, Universitaetsklinikum Heidelberg, Heidelberg, Germany.
authors.forename: Niels
authors.initials: N
authors.lastname: Weinhold
authors.forename: Jerome
authors.initials: J
authors.lastname: Moreaux
authors.forename: Marc S
authors.initials: MS
authors.lastname: Raab
authors.forename: Dirk
authors.initials: D
authors.lastname: Hose
authors.forename: Thomas
authors.initials: T
authors.lastname: Hielscher
authors.forename: Axel
authors.initials: A
authors.lastname: Benner
authors.forename: Tobias
authors.initials: T
authors.lastname: Meissner
authors.forename: Edith
authors.initials: E
authors.lastname: Ehrbrecht
authors.forename: Michaela
authors.initials: M
authors.lastname: Brough
authors.forename: Anna
authors.initials: A
authors.lastname: Jauch
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.forename: Bernard
authors.initials: B
authors.lastname: Klein
authors.forename: Marion
authors.initials: M
authors.lastname: Moos
mesh_terms: D000782:Aneuploidy; D002869:Chromosome Aberrations; D002895:Chromosomes, Human, Pair 5; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009101:Multiple Myeloma / Q000235:genetics* / Q000378:metabolism; D016254:Mutagenesis, Insertional; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D000090243:Nucleophosmin; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism; D018709:Statistics, Nonparametric; D015854:Up-Regulation
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D012269:Ribosomal Proteins; D000090243:Nucleophosmin