Burkitt Lymphoma

Identification and analysis of genes deregulated through chromosomal rearrangements in Burkitt lymphoma

Burkitt lymphoma is a highly aggressive entity of the non-Hodgkin lymphomas, and accounts for app. 2% of the lymphomas in humans. This malignancy can be subdivided into three subtypes: childhood, sporadic and immunodeficiency associated Burkitt lymphomas. One further characterization of the childhood form is often an association with Epstein-Barr virus infection. Like many other leukemias and lymphomas, chromosomal rearrangements appear to play a major role in Burkitt lymphoma; The cytogenetic hallmark being the translocation t(8;14) which juxtaposes the immunoglobulin heavy chain promoter region in front of the MYC oncogene and is found in nearly all classical cases of Burkitt-lymphoma. In addition, other chromosomal abnormalities have also been identified and the deregulation of genes in these regions have been proposed as possibly affecting patient survival.
As a member of the German network “Molecular Mechanisms in Malignant Lymphoma”, our goal is to study the role of non-MYC associated gene rearrangements in Burkitt and other non-Hodgkin lymphomas, and to analyze the genes influenced by these rearrangements for their effects on lymphoma proliferation, differentiation and viability. In the end, the concept of this approach is the identification of genes associated with key pathways, whose modulation might lead to an increase in survival for lymphoma patients. Methods used to fulfil these goals are array comparative genome hybridization (array-CGH), in order to identify chromosomal abnormalities, microarray analysis in order to identify genes either highly or weakly expressed in the rearranged regions, and the bivalent recombinase mediated cassette exchange (RCME) strategy, either for RNAi mediated knockdown of genes strongly over-expressed in regions of chromosomal gains or for complementation of weakly expressed genes coded on deleted regions. The effects of these gene modulations are then further analyzed by proliferation and viability assays as well as by further microarray analysis in order to delineate pathways involved in the maintenance of the tumor phenotype.



Collaborations
Dr. Sven Wessendorf, Innere Medizin III, Universitätsklinik Ulm