Objective 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. Fields of science medical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesgeneticschromosomes Keywords 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) Topic(s) ERC-SG-LS3 - ERC Starting Grant - Cellular and Developmental Biology Call for proposal ERC-2007-StG See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III (F.S.P.) EU contribution € 893 038,52 Address CALLE MELCHOR FERNANDEZ ALMAGRO 3 28029 Madrid Spain See on map Region Comunidad de Madrid Comunidad de Madrid Madrid Activity type Research Organisations Principal investigator Almudena Ramiro (Dr.) Administrative Contact Luzma García (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (2) Sort alphabetically Sort by EU Contribution Expand all Collapse all CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III (F.S.P.) Spain EU contribution € 893 038,52 Address CALLE MELCHOR FERNANDEZ ALMAGRO 3 28029 Madrid See on map Region Comunidad de Madrid Comunidad de Madrid Madrid Activity type Research Organisations Principal investigator Almudena Ramiro (Dr.) Administrative Contact Luzma García (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data FUNDACION SECTOR PUBLICO ESTATAL CENTRO NACIONAL INVESTIGACIONES ONCOLOGICAS CARLOS III Participation ended Spain EU contribution € 702 961,48 Address C MELCHOR FERNANDEZ ALMAGRO 3 28029 Madrid See on map Region Comunidad de Madrid Comunidad de Madrid Madrid Activity type Research Organisations Administrative Contact Laura Bertolini (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data