Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types

MALT B cell lymphomas with t(1;14)(p22;q32) showed a recurrent breakpoint u pstream 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 caspa se recruitment domain (CARD) homologous to that found in several apoptotic molecules. Bcl10 and E10 activated NF-KB but caused apoptosis of 293 cells. Bcl10 expressed in a MALT lymphoma exhibited a frameshift mutation resulti ng in truncation distal to the CARD. Truncated Bcl10 activated NF-KB but di d not induce apoptosis. Wild-type Bcl10 suppressed transformation, whereas mutant forms had lost this activity and displayed gain-of-function transfor ming activity. Similar mutations were detected in other tumor types, indica ting that Bcl10 may be commonly involved in the pathogenesis of human malig nancy.