Aggressive mucosa associated lymphoid tissue lymphomas are associated with mutations in Bcl10

MALT B cell lymphomas with t(1;14)(p22;q32) showed a recurrent breakpoint upstream of the promoter of a novel gene, BcL10. Bcl10 is a cellular homoLog of the equine herpesvirus-2 E10 gene: both contain an amino-terminal caspase recruitment domain (CARD) homologous to that found in several apoptotic molecules, Bcl10 and E10 activated NF-kappa B but caused apoptosis of 293 cells. Bcl10 expressed in a MALT lymphoma exhibited a frameshift mutation resulting in truncation distal to the CARD. Truncated Bcl10 activated NF-kappa B but did not induce apoptosis, Wild-type Bcl10 suppressed transformation, whereas: mutant forms had lost this activity and displayed gain-of-function transforming activity. Similar mutations Were detected in other tumor types, indicating that Bcl10 may be commonly involved in the pathogenesis of human malignancy.