title: Distinct Patterns of Colocalization of the CCND1 and CMYC Genes With Their Potential Translocation Partner IGH at Successive Stages of B-Cell Differentiation.
abstract: The immunoglobulin heavy chain (IGH) locus is submitted to intra-chromosomal DNA breakages and rearrangements during normal B cell differentiation that create a risk for illegitimate inter-chromosomal translocations leading to a variety of B-cell malignancies. In most Burkitt's and Mantle Cell lymphomas, specific chromosomal translocations juxtapose the IGH locus with a CMYC or Cyclin D1 (CCND1) gene, respectively. 3D-fluorescence in situ hybridization was performed on normal peripheral B lymphocytes induced to mature in vitro from a naive state to the stage where they undergo somatic hypermutation (SHM) and class switch recombination (CSR). The CCND1 genes were found very close to the IGH locus in naive B cells and further away after maturation. In contrast, the CMYC alleles became localized closer to an IGH locus at the stage of SHM/CSR. The colocalization observed between the two oncogenes and the IGH locus at successive stages of B-cell differentiation occurred in the immediate vicinity of the nucleolus, consistent with the known localization of the RAGs and AID enzymes whose function has been demonstrated in IGH physiological rearrangements. We propose that the chromosomal events leading to Mantle Cell lymphoma and Burkitt's lymphoma are favored by the colocalization of CCND1 and CMYC with IGH at the time the concerned B cells undergo VDJ recombination or SHM/CSR, respectively. J. Cell. Biochem. 117: 1506-1510, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: UMR8126, CNRS, Université Paris-Sud, Institut de Cancérologie Gustave Roussy, Villejuif, France.|LIA1066, Laboratoire Franco-Russe de Recherche en Oncologie, Villejuif, France.|Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Ilya
authors.initials: I
authors.lastname: Sklyar
authors.affiliation: UMR8126, CNRS, Université Paris-Sud, Institut de Cancérologie Gustave Roussy, Villejuif, France.|LIA1066, Laboratoire Franco-Russe de Recherche en Oncologie, Villejuif, France.|Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Olga V
authors.initials: OV
authors.lastname: Iarovaia
authors.affiliation: LIA1066, Laboratoire Franco-Russe de Recherche en Oncologie, Villejuif, France.|Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Gavrilov
authors.affiliation: UMR8126, CNRS, Université Paris-Sud, Institut de Cancérologie Gustave Roussy, Villejuif, France.|LIA1066, Laboratoire Franco-Russe de Recherche en Oncologie, Villejuif, France.|Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russia.
authors.forename: Andrey
authors.initials: A
authors.lastname: Pichugin
authors.affiliation: UMR8126, CNRS, Université Paris-Sud, Institut de Cancérologie Gustave Roussy, Villejuif, France.|LIA1066, Laboratoire Franco-Russe de Recherche en Oncologie, Villejuif, France.|Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russia.
authors.forename: Diego
authors.initials: D
authors.lastname: Germini
authors.affiliation: UMR8126, CNRS, Université Paris-Sud, Institut de Cancérologie Gustave Roussy, Villejuif, France.|LIA1066, Laboratoire Franco-Russe de Recherche en Oncologie, Villejuif, France.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Tsfasman
authors.affiliation: INSERM U917, Université de Rennes, Rennes, France.
authors.forename: Gersende
authors.initials: G
authors.lastname: Caron
authors.affiliation: INSERM U917, Université de Rennes, Rennes, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Fest
authors.affiliation: UMR8126, CNRS, Université Paris-Sud, Institut de Cancérologie Gustave Roussy, Villejuif, France.|LIA1066, Laboratoire Franco-Russe de Recherche en Oncologie, Villejuif, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Lipinski
authors.affiliation: LIA1066, Laboratoire Franco-Russe de Recherche en Oncologie, Villejuif, France.|Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia.|Faculty of Biology, M.V. Lomonosov Moscow State University, 119992 Moscow, Russia.
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Razin
authors.affiliation: UMR8126, CNRS, Université Paris-Sud, Institut de Cancérologie Gustave Roussy, Villejuif, France.|LIA1066, Laboratoire Franco-Russe de Recherche en Oncologie, Villejuif, France.|Faculty of Biology, M.V. Lomonosov Moscow State University, 119992 Moscow, Russia.
authors.forename: Yegor S
authors.initials: YS
authors.lastname: Vassetzky
mesh_terms: D000483:Alleles; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000502:physiology*; D056426:Genetic Loci / Q000502:physiology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D017404:In Situ Hybridization, Fluorescence; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*
chemical_list: C530104:CCND1 protein, human; D007143:Immunoglobulin Heavy Chains; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D019938:Cyclin D1
keywords: B-CELL LYMPHOMA; CCND1; CMYC; IGH; ILLEGITIMATE RECOMBINATION; NUCLEAR ORGANIZATION