Microarray ANALYSIS of t(11;18)(Q21;Q21)-positive and -negative gastrointestinal MALT lymphomas.

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e14610 Background: Among the genetic abnormalities that occur in MALT lymphomas, the translocation t(11;18) is of particular interest because it is predominantly documented in MALT lymphomas of the gut. It results in the creation of a fusion protein API2-MALT1 that activates the transcription factor NF-kB via enhanced IKKγ polyubiquitination. Here, we apply microarray analysis to identify differentially expressed genes related to the pathogenesis of gastrointestinal (GI) MALT lymphomas. Methods: 8 t(11;18)-positive and 6 t(11;18)-negative GI MALT lymphomas were compared with normal lymphoid by microarray (Affymetrix Plus 2.0 Gene Chip). 6 splenectomy specimens (with a prominent marginal zone but without obvious morphologic anomalies) of healthy individuals suffering from traumatic splenic rupture were selected as reference tissue, as the marginal zone is assumed to be the non-tumoural counterpart of MALT lymphomas. For this particular study, the number of representative cases documented with both surgical resection specimens and frozen tissue (as required for gene expression profiling) is limited, due to the current conservative treatment of GI MALT lymphomas (the majority of gastric lymphomas regresses after Helicobacter pylori eradication therapy). Results: By comparing the 8 t(11;18)-positive MALT lymphomas as well as their 6 t(11;18)-negative counterparts to normal lymphoid tissue (e.g. spleen with prominent marginal zones), we could define a common GI MALT lymphoma signature, most likely comprising the genes with significance in the development of type of cancer. Moreover, unsupervised analysis of the gene expression profiles of these fourteen GI MALT lymphomas clustered in 2 groups, with the clustering being determined by presence or absence of the API2-MALT1 fusion protein. The latter finding suggests different pathways for both t(11;18)-positive and -negative GI MALT lymphomas. Interestingly, within the group of t(11;18)-positive GI MALT lymphomas, there was a tendency that the gene expression profiles of these tumours tended to cluster according to the location of the MALT1 breakpoint. Conclusions: Our study reveals several genes that play an important rol in MALT lymphomagenesis. No significant financial relationships to disclose.