Analyse des genomischen Status der Proto-Onkogene c-Rel und BCL11A sowie deren RNA- und Proteinexpression in Marginalzonen-B-Zell-Lymphomen und diffus großzelligen B-Zell-Lymphomen des Gastrointestinaltraktes

Abstract

Amplifications of the c-Rel locus on chromosome 2p13-p16 have been described in distinct lymphoma subtypes, most notably in mediastinal diffuse large B cell lymphoma (DLBCL) and classical Hodgkin´s lymphoma. In B cell lymphomas of the gastrointestinal tract gains of chromosomal material in chromosomal region 2p13-p16 could also be detected using comparative genomic hybridization (CGH). Candidate genes for lymphomagenesis in this region are c-Rel and BCL11A. The objective of this work was to shape out a potential gene dosis effect. For this purpose, 13 lymphomas of the gastrointestinal tract (8 diffuse large cell B cell lymphoma and 5 marginal zone B cell lymphoma) have been analyzed for their genomic status of c-Rel and BCL11A using fluorescence in situ hybridization (FISH). For 3 out of 13 lymphomas a gain of chromosomal material in chromosomal region 2p13-p16 had been detected. By using FISH a gain of gene number copies could be detected 5 lymphomas (3 of which had known gains of chromosomal material in CGH). The relative expression of c-Rel and BCL mRNA was detected using quantitative real time PCR. Furthermore, the expression and intracellular localization of the c-Rel and BCL11A protein were confirmed by using immunohistochemical staining with antibodies not commercially available. There was evidence for a stringen t gene dosis effect of c-Rel and BCL11A in only 2 out of 13 lymphomas. The remaining lymphomas present a heterogenous expression pattern. Maybe there are other regulatory mechanisms leading to constitutive activation of c-Rel and/ or BCL11A.