Mucosa-associated lymphoid tissue (
MALT) lymphoma is characterized by t(11;18)(q21;q21)/API2-MALT1, t(1;14)(p22;q32)/BCL10-IGH and t(14;18)(q32;q21)/IGH-MALT1, which commonly activate the nuclear factor (
NF)-kappaB pathway. Gastric
MALT lymphomas harboring such translocations usually do not respond to Helicobacter pylori eradication, while most of those without translocation can be cured by
antibiotics. To understand the molecular mechanism of these different
MALT lymphoma subgroups, we performed gene expression profiling analysis of 21
MALT lymphomas (13 translocation-positive, 8 translocation-negative). Gene set enrichment analysis (GSEA) of the
NF-kappaB target genes and 4394 additional gene sets covering various cellular pathways, biological processes and molecular functions have shown that translocation-positive
MALT lymphomas are characterized by an enhanced expression of
NF-kappaB target genes, particularly
toll like receptor (TLR)6,
chemokine, CC motif, receptor (CCR)2, cluster of differentiation (CD)69 and B-cell CLL/
lymphoma (BCL)2, while translocation-negative cases were featured by active inflammatory and immune responses, such as
interleukin-8, CD86, CD28 and inducible T-cell costimulator (ICOS). Separate analyses of the genes differentially expressed between translocation-positive and -negative cases and measurement of gene ontology term in these differentially expressed genes by hypergeometric test reinforced the above findings by GSEA. Finally, expression of TLR6, in the presence of TLR2, enhanced both API2-MALT1 and BCL10-mediated
NF-kappaB activation in vitro. Our findings provide novel insights into the molecular mechanism of
MALT lymphomas with and without translocation, potentially explaining their different clinical behaviors.