title: 1q12 chromosome translocations form aberrant heterochromatic foci associated with changes in nuclear architecture and gene expression in B cell lymphoma.
abstract: Epigenetic perturbations are increasingly described in cancer cells where they are thought to contribute to deregulated gene expression and genome instability. Here, we report the first evidence that a distinct category of chromosomal translocations observed in human tumours--those targeting 1q12 satellite DNA--can directly mediate such perturbations by promoting the formation of aberrant heterochromatic foci (aHCF). By detailed investigations of a 1q12 translocation to chromosome 2p, in a case of human B cell lymphoma, aberrant aHCF were shown to be localized to the nuclear periphery and to arise as a consequence of long range 'pairing' between the translocated 1q12 and chromosome 2 centromeric regions. Remarkably, adjacent 2p sequences showed increased levels of repressive histone modifications, including H4K20me3 and H3K9me3, and were bound by HP1. aHCF were associated to aberrant spatial localization and deregulated expression of a novel 2p gene (GMCL1) that was found to have prognostic impact in diffuse large B cell lymphoma. Thus constitutive heterochromatin rearrangements can contribute to tumourigenesis by perturbing gene expression via long range epigenetic mechanisms.
authors.affiliation: INSERM U823, Institut Albert Bonniot, Grenoble, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Fournier
authors.forename: Anne
authors.initials: A
authors.lastname: McLeer-Florin
authors.forename: Christine
authors.initials: C
authors.lastname: Lefebvre
authors.forename: Samuel
authors.initials: S
authors.lastname: Duley
authors.forename: Leila
authors.initials: L
authors.lastname: Barki
authors.forename: Juliana
authors.initials: J
authors.lastname: Ribeyron
authors.forename: Kassambara
authors.initials: K
authors.lastname: Alboukadel
authors.forename: Sieme
authors.initials: S
authors.lastname: Hamaidia
authors.forename: Aurélie
authors.initials: A
authors.lastname: Granjon
authors.forename: Rémy
authors.initials: R
authors.lastname: Gressin
authors.forename: Alicia
authors.initials: A
authors.lastname: Lajmanovich
authors.forename: Thierry
authors.initials: T
authors.lastname: Bonnefoix
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Chauvelier
authors.forename: Alexandra
authors.initials: A
authors.lastname: Debernardi
authors.forename: Sophie
authors.initials: S
authors.lastname: Rousseaux
authors.forename: Florence
authors.initials: F
authors.lastname: de Fraipont
authors.forename: Martin
authors.initials: M
authors.lastname: Figeac
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Kerckaert
authors.forename: John
authors.initials: J
authors.lastname: De Vos
authors.forename: Yves
authors.initials: Y
authors.lastname: Usson
authors.forename: Katia
authors.initials: K
authors.lastname: Delaval
authors.forename: Alexei
authors.initials: A
authors.lastname: Grichine
authors.forename: Claire
authors.initials: C
authors.lastname: Vourc'h
authors.forename: Saadi
authors.initials: S
authors.lastname: Khochbin
authors.forename: Robert
authors.initials: R
authors.lastname: Feil
authors.forename: Dominique
authors.initials: D
authors.lastname: Leroux
authors.forename: Mary B
authors.initials: MB
authors.lastname: Callanan
mesh_terms: D002467:Cell Nucleus / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006570:Heterochromatin / Q000235:genetics*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics*; D014178:Translocation, Genetic
chemical_list: D006570:Heterochromatin