Abstract 4947: HACE1 is a putative tumor suppressor gene in B-cell lymphomagenesis down-regulated by both deletion and epigenetic mechanisms
In: AACR 106th Annual Meeting 2015 ; https://hal-univ-rennes1.archives-ouvertes.fr/hal-01300808 ; AACR 106th Annual Meeting 2015, Apr 2015, Philadelphia, PA, United States. 75 (15 Supplement), pp.4947--4947, 2015
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Zugriff:
International audience ; HACE1, located on chromosome 6q, encodes an E3 ubiquitin ligase and is downregulated in human tumors such as neuroblastomas and natural killer (NK) lymphomas. HACE1 has been shown to ubiquitylate Rac1, a protein involved in cell proliferation and G2/M cell cycle progression. The function of HACE1 and the factors involved in its transcriptional regulation are largely unknown in the context of B-cell lymphomas. We show here, by RT-qPCR, that HACE1 gene is constitutively expressed in Normal lymph nodes and in normal B-cells isolated from peripheral blood, contrasting with a strong downregulation of its expression in more than 70% (77/111) of diffuse large B-cell lymphoma (DLBCL) cases and in four tested B-Lymphoma cell lines. HACE1 gene copy number was assessed by quantitative multiplex PCR of short fluorescent fragments (QMPSF) and array for comparative genomic hybridization (aCGH) in 91 DLBCL cases. A HACE1 heterozygous deletion was observed in 38.1% and an homozygous deletion in 2.4% of cases. These deletions were associated with a significant gene expression decrease. The molecular epigenetic mechanisms underlying HACE1 downregulation were also investigated. Using pyrosequencing assays, as compared to normal B-cells, we observed an hypermethylation of HACE1 promoter CpG177 island in 60% (68/111) of DLBCL cases and in all tested B-Lymphoma cell lines. However, no significant correlation between promoter methylation status and gene expression level was demonstrated. Furthermore, RT-qPCR assays revealed that the demethylating agent 5′azacytidine (5′AZA) did not induce a HACE1 gene expression increase in the different cell lines. By contrast, the histone deacetylase inhibitors (HDACi) trichostatin A (TSA) and LBH589 strongly reactivated the expression of HACE1 in Ramos, Raji and RL cells in which the CpG 177 island was fully methylated. We next performed ChIP experiments to determine whether HACE1 locus chromatin was in an active or inactive conformation in Ramos cell line, the most ...
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Abstract 4947: HACE1 is a putative tumor suppressor gene in B-cell lymphomagenesis down-regulated by both deletion and epigenetic mechanisms
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Autor/in / Beteiligte Person: | Bouzelfen, Abdelilah ; Alcantara, Marion ; Kora, Hafid ; Bertrand, Philippe ; Mareschal, Sylvain ; Bohers, Elodie ; Maingonnat, Catherine ; Ruminy, Philippe ; ADRIOUCH, Sahil ; Riou, Gaetan ; Figeac, Martin ; Fest, Thierry ; Bastard, Christian ; Tilly, Hervé ; Latouche, Jean-Baptiste ; Jardin, Fabrice ; Groupe d'étude des proliférations lymphoïdes (GPL) ; Université de Rouen Normandie (UNIROUEN) ; Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM) ; Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND) ; Génétique du cancer et des maladies neuropsychiatriques (GMFC) ; Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes ; Plateforme de génomique fonctionnelle et structurelle Lille ; Institut pour la recherche sur le cancer de Lille Lille (IRCL)-Université de Lille, Droit et Santé ; Microenvironnement et cancer (MiCa) ; Université de Rennes 1 (UR1) ; Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) |
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Zeitschrift: | AACR 106th Annual Meeting 2015 ; https://hal-univ-rennes1.archives-ouvertes.fr/hal-01300808 ; AACR 106th Annual Meeting 2015, Apr 2015, Philadelphia, PA, United States. 75 (15 Supplement), pp.4947--4947, 2015 |
Veröffentlichung: | HAL CCSD, 2015 |
Medientyp: | Konferenz |
DOI: | 10.1158/1538-7445.AM2015-4947 |
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