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1q12 chromosome translocations form aberrant heterochromatic foci associated with changes in nuclear architecture and gene expression in B cell lymphoma.

By Alexandra Fournier, Anne Mcleer-Florin, Christine Lefebvre, Samuel Duley, Leila Barki, Juliana Ribeyron, Kassambara Alboukadel, Sieme Hamaidia, Aurélie Granjon, Rémy Gressin, Alicia Lajmanovich, Thierry Bonnefoix, Stéphanie Chauvelier, Alexandra Debernardi, Sophie Rousseaux, Florence De Fraipont, Martin Figeac, Jean-Pierre Kerckaert, John De Vos, Yves Usson, Katia Delaval, Alexei Grichine, Claire Vourc'H, Saadi Khochbin, Robert Feil, Dominique Leroux and Mary Callanan


International audienceEpigenetic 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

Topics: B cell lymphoma, GMCL1, heterochromatic foci, nuclear architecture, 1q12 pericentric heterochromatin, MESH: Cell Nucleus, MESH: Chromosomes, Human, Pair 1, MESH: Chromosomes, Human, Pair 2, MESH: Gene Expression Regulation, Neoplastic, MESH: Heterochromatin, MESH: Humans, MESH: Lymphoma, B-Cell, MESH: Translocation, Genetic, [SDV.GEN]Life Sciences [q-bio]/Genetics
Publisher: 'Wiley'
Year: 2010
DOI identifier: 10.1002/emmm.201000067
OAI identifier: oai:HAL:inserm-00482580v1
Provided by: HAL-Pasteur
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