PMID: identifiant
de la référence Pubmed : |
 |
 (20432501)  |
|
| titre : |
|
1q12 chromosome translocations form aberrant heterochromatic foci associated with changes in nuclear architecture and gene expression in B cell lymphoma. |
|
| auteur(s) : |
|
Alexandra Fournier1, Anne Mcleer-Florin1, 2, Christine Lefebvre1, 2, Samuel Duley1, Leila Barki1, Juliana Ribeyron1, Kassambara Alboukadel1, Sieme Hamaidia1, Aurélie Granjon1, Rémy Gressin1, 2, Alicia Lajmanovich1, 3, Thierry Bonnefoix1, 3, Stéphanie Chauvelier1, Alexandra Debernardi1, Sophie Rousseaux1, Florence De Fraipont1, 4, Martin Figeac5, Jean-Pierre Kerckaert6, John De Vos7, Yves Usson8, Katia Delaval9, Alexei Grichine1, Claire Vourc'H1, Saadi Khochbin1, Robert Feil9, Dominique Leroux1, 2, Mary Callanan ( ) 1, 2 |
|
| laboratoire : |
|
|
|
| Équipe de recherche : |
|
INSERM U823, équipe 5 (cibles diagnostiques ou thérapeutiques et vectorisation de drogues dans le cancer du poumon)
INSERM U823, équipe 10 (Stress et Dynamique de l'Organisation du Génome)
INSERM U823, équipe 6 (Epigénétique et Signalisation Cellulaire)
INSERM U823, équipe 7 (Voies Oncogéniques Des Hémopathies Malignes) |
| résumé : |
|
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. |
|
| domaine : |
|
Sciences du Vivant/Génétique
|
|
langue du texte
intégral : |
|
Anglais |
|
| ISSN : |
|
1757-4676 |
|
|
| type de publication : |
|
Articles dans des revues avec comité de lecture |
|
| DOI : |
|
10.1002/emmm.201000067 |
|
| journal : |
|
| EMBO Molecular Medicine (EMBO Mol Med) |
| Publisher |
Wiley Open Access |
| ISSN |
1757-4676 (eISSN : 1757-4684) |
|
|
| Audience : |
|
internationale |
|
| date de publication : |
|
05/2010 |
|
date de publication
électronique : |
|
29/04/2010 |
|
| volume : |
|
2 |
|
| numéro : |
|
5 |
|
| page, identifiant, ... : |
|
159-71 |
|
|
| mots-clés auteur : |
|
B cell lymphoma – GMCL1 – heterochromatic foci – nuclear architecture – 1q12 pericentric heterochromatin |
|
| Descripteur(s) MeSH : |
|
Cell Nucleus – Chromosomes – Human – Pair 1 – Pair 2 – Gene Expression Regulation – Neoplastic – Heterochromatin – Humans – Lymphoma – B-Cell – Translocation – Genetic |
|
| contrat, financement : |
|
Funding was from the Fondation de France, the Institut National du Cancer (EpiPro network, the programme 'Developpement de plateformes hospitalières de génétique moléculaire des cancers', the P.A.I.R 'Mantle Cell Lymphoma network' and the INCa-DHOS translational research programme 'CT-Lymph'). Additional funding was obtained from the Région Rhone-Alpes programme 'Thématique prioritaire--Cancer', the canceropôle CLARA (EpiMed), the Ligue Nationale Contre le Cancer (LNCC)--Comités de l'Isère/Savoie, the Délegation Régionale de la Recherche Clinique--CHU de Grenoble, the French GOELAMS clinical trials group and the ARAMIS association. AD and JBR have been recruited through the INCa-DHOS 'CT-Lymph' program. AF has been the recipient of doctoral funding from the Ministère de l'Enseignement Supérieur et de la Recherche, the Association pour la Recherche sur le Cancer (ARC) and the Société Française d'Hématologie (SFH); AMLF of post-doctoral funding from the ARC-ARECA network 'epigenetic profiling in breast and haematological tumours'; LB of doctoral funding from the Ministère de l'Enseignement Supérieur et de la Recherche and the LNCC; MC of a Contrat d'Interface INSERM/Grenoble University Hospital Centre (2006-2011). Affymetrix microarrays were processed in the Microarray Core Facility of the Institute of Research on Biotherapy, CHRU-INSERM-UM1 Montpellier, http://irb.chu-montpellier.fr/ |
|
