title: Differential nuclear organization of translocation-prone genes in nonmalignant B cells from patients with t(14;16) as compared with t(4;14) or t(11;14) myeloma.
abstract: Gene organization in nonmalignant B cells from t(4;14) and t(11;14) multiple myeloma (MM) patients differs from that of healthy donors. Among recurrent IGH translocations in MM, the frequency of t(4;14) (IGH and FGFR3) or t(11;14) (IGH and CCND1) is greater than the frequency of t(14;16) (IGH and MAF). Gene organization in t(14;16) patients may influence translocation potential of MAF with IGH. In patients, three-dimensional FISH revealed the positions of IGH, CCND1, FGFR3, and MAF in nonmalignant B cells that are likely similar to those when MM first arose, compared with B cells from healthy donors. Overall, IGH occupies a more central nuclear position while MAF is more peripherally located. However, for B cells from t(4;14) and t(11;14) patients, IGH and FGFR3, or IGH and CCND1 are found in spatial proximity: IGH and MAF are not. This differs in B cells from t(14;16) patients and healthy donors where IGH is approximately equidistant to FGFR3, CCND1, and MAF, suggesting that gene organization in t(14;16) patients is different from that in t(4;14) or t(11;14) patients. Translocations between IGH and MAF may arise only in the absence of close proximity to the more frequent partners, as appears to be the case for individuals who develop t(14;16) MM.
authors: Department of Oncology, University of Alberta and Cross Cancer Institute, Edmonton, Alberta, Canada.
authors: Lorri D
authors: LD
authors: Martin
authors: Jana
authors: J
authors: Harizanova
authors: Christiaan H
authors: CH
authors: Righolt
authors: George
authors: G
authors: Zhu
authors: Sabine
authors: S
authors: Mai
authors: Andrew R
authors: AR
authors: Belch
authors: Linda M
authors: LM
authors: Pilarski
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D056426:Genetic Loci; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D009101:Multiple Myeloma / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D051257:Proto-Oncogene Proteins c-maf / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C529133:IGH-CCND1 fusion protein, human; D007143:Immunoglobulin Heavy Chains; C495607:MAF protein, human; D015514:Oncogene Proteins, Fusion; D051257:Proto-Oncogene Proteins c-maf; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II