title: Simultaneous translocations of FGFR3/MMSET and CCND1 into two different IGH alleles in multiple myeloma: lack of concurrent activation of both proto-oncogenes.
abstract: The simultaneous occurrence of two different translocations affecting both alleles of the IGH gene has rarely been reported in multiple myeloma. In such a case, two different oncogenes might become transcriptionally deregulated. To investigate this hypothesis, we have characterized the plasma cell leukemia cell line SK-MM2 and a primary myeloma both carrying simultaneous IGH-FGFR3/MMSET and IGH-CCND1 fusions as shown by multicolor fluorescence in situ hybridization. Remarkably, quantitative real-time polymerase chain reaction demonstrated that only one of the oncogene loci was transcriptionally upregulated in both instances. Moreover, the upregulated oncogenes differed between both samples. Thus, biallelic IGH translocations might exert different pathogenetic effects in plasma cell disorders.
authors.affiliation: Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany. bsaezoch@alumni.unav.es
authors.forename: Borja
authors.initials: B
authors.lastname: Sáez
authors.forename: José I
authors.initials: JI
authors.lastname: Martín-Subero
authors.forename: Idoya
authors.initials: I
authors.lastname: Lahortiga
authors.forename: Cristina
authors.initials: C
authors.lastname: Largo
authors.forename: María J
authors.initials: MJ
authors.lastname: Larrayoz
authors.forename: María D
authors.initials: MD
authors.lastname: Odero
authors.forename: Felipe
authors.initials: F
authors.lastname: Prosper
authors.forename: Juan C
authors.initials: JC
authors.lastname: Cigudosa
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: María J
authors.initials: MJ
authors.lastname: Calasanz
mesh_terms: D000483:Alleles; D002460:Cell Line; D002871:Chromosome Banding; D020223:Chromosome Painting; D056741:Cyclin D; D016213:Cyclins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007621:Karyotyping; D009101:Multiple Myeloma / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic
chemical_list: D056741:Cyclin D; D016213:Cyclins; D007143:Immunoglobulin Heavy Chains; D012333:RNA, Messenger; D012097:Repressor Proteins; D011495:Histone-Lysine N-Methyltransferase; C419586:NSD2 protein, human; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3