Objectif Most of the lymphomas diagnosed in the western world are originated from mature B cells. The hallmark of these malignancies is the presence of recurrent chromosome translocations that usually involve the immunoglobulin loci and a proto-oncogene. As a result of the translocation event the proto-oncogene becomes deregulated under the influence of immunoglobulin cis sequences thus playing an important role in the etiology of the disease. Upon antigen encounter mature B cells engage in the germinal center reaction, a complex differentiation program of critical importance to the development of the secondary immune response. The germinal center reaction entails the somatic remodelling of immunoglobulin genes by the somatic hypermutation and class switch recombination reactions, both of which are triggered by Activation Induced Deaminase (AID). We have previously shown that AID also initiates lymphoma-associated c-myc/IgH chromosome translocations. In addition, the germinal center reaction involves a fine-tuned balance between intense B cell proliferation and program cell death. This environment seems to render B cells particularly vulnerable to malignant transformation. We aim at studying the molecular events responsible for B cell susceptibility to lymphomagenesis from two perspectives. First, we will address the role of AID in the generation of lymphomagenic lesions in the context of AID specificity and transcriptional activation. Second, we will approach the regulatory function of microRNAs of AID-dependent, germinal center events. The proposal aims at the molecular understanding of a process that lies in the interface of immune regulation and oncogenic transformation and therefore the results will have profound implications both to basic and clinical understanding of lymphomagenesis. Champ scientifique medical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesgeneticschromosomes Mots‑clés germinal center hypermutation lymphoma microRNA translocation Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-SG-LS3 - ERC Starting Grant - Cellular and Developmental Biology Appel à propositions ERC-2007-StG Voir d’autres projets de cet appel Régime de financement ERC-SG - ERC Starting Grant Institution d’accueil CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III (F.S.P.) Contribution de l’UE € 893 038,52 Adresse CALLE MELCHOR FERNANDEZ ALMAGRO 3 28029 Madrid Espagne Voir sur la carte Région Comunidad de Madrid Comunidad de Madrid Madrid Type d’activité Research Organisations Chercheur principal Almudena Ramiro (Dr.) Contact administratif Luzma García (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (2) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III (F.S.P.) Espagne Contribution de l’UE € 893 038,52 Adresse CALLE MELCHOR FERNANDEZ ALMAGRO 3 28029 Madrid Voir sur la carte Région Comunidad de Madrid Comunidad de Madrid Madrid Type d’activité Research Organisations Chercheur principal Almudena Ramiro (Dr.) Contact administratif Luzma García (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée FUNDACION SECTOR PUBLICO ESTATAL CENTRO NACIONAL INVESTIGACIONES ONCOLOGICAS CARLOS III Participation terminée Espagne Contribution de l’UE € 702 961,48 Adresse C MELCHOR FERNANDEZ ALMAGRO 3 28029 Madrid Voir sur la carte Région Comunidad de Madrid Comunidad de Madrid Madrid Type d’activité Research Organisations Contact administratif Laura Bertolini (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
