Aggressive mucosa associated lymphoid tissue lymphomas are associated with mutations inBcl10

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Abstract
Structurally, wild type Bcl10 protein consists of a caspase recruitment domain (CARD), which has significant homology with other known CARDs,7 and a novel distal amino acid sequence. Caspases are involved in the apoptotic pathway8 and it was hypothesised that Bcl10 could be functionally associated with this process, though CARD proteins can be either pro- or anti-apoptotic. In functional assays, wild type Bcl10 was shown to be weakly pro-apoptotic and it could also activate nuclear factor (NF) κB. Activation of NF-κB, a DNA binding factor, is the ultimate goal of many intracellular signalling pathways, and the consequence is considered to be pro-inflammatory.9 It was shown that, like p53, which is probably the most widely investigated tumour suppressor gene implicated in many malignant processes, wild typeBcl10 had tumour suppressor activity as it could inhibit cellular transformation by oncogenes in vitro. In contrast, the truncated Bcl10 mutants used by the aggressive MALT lymphoma variant had notably different properties in some of these assays, though they retained the capability to activate NF-κB. Truncated Bcl10 was no longer pro-apoptotic, and not only did it fail to have tumour suppressor activity, evidence was presented that it has tumorigenic properties.