High-resolution genomic profiling of marginal zone B-cell lymphomas and variants

We studied marginal zone B-cell lymphomas of the gastrointestinal tract including seven small cell MALT lymphomas, eight composite lymphomas and thirteen large cell variants using SNP-array profiling. We found an increase of genomic complexity with lymphoma progression, and could identify gains of prominent (proto)oncogenes REL, ETS1, PTPN1, PTEN and KRAS that were associated exclusively with the large cell presentation of MALT lymphoma. Losses of ADAM3A and SCAPER, as well as gains of SIRPB1 occur during progression from small cell to large cell lymphoma. In two case studies, we examined lymphoma progression comparing two different regions of the same tumor and material acquired at two different time points from another lymphoma. Our analyses reveal genomic heterogeneity in both cases, supporting the theory of an oligoclonal tumor evolution model for MALT lymphomas and its variants. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved tumor samples. Copy number and loss of heterozygosity analysis of Affymetrix GenomeWide SNP 6.0 arrays was performed for 7 small cell MALT lymphomas, 8 large cell areas of Composite lymphomas and 13 large cell variants. Two independant hybridizations of one of the small cell MALT lymphoma and one of the large cell areas of Composite lymphoma Samples were performed.