Qg. Zhang et al., Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32), NAT GENET, 22(1), 1999, pp. 63-68
Mucosa-associated lymphoid tissue (MALT) lymphomas most frequently involve
the gastrointestinal tract and are the most common subset of extranodal non
-Hodgkin lymphoma(1) (NHL). Here we describe overexpression of BCL10, a nov
el apoptotic signalling gene that encodes an amino-terminal caspase recruit
ment domain (CARD; ref. 2), in MALT lymphomas due to the recurrent t(1;14)(
p22;q32) (ref. 3). BCL10 cDNAs from t(1;14)-positive MALT tumours contained
a variety of mutations, most resulting in truncations either in or carboxy
terminal to the CARD. Wild-type BCL10 activated NF-kappa B but induced apo
ptosis of MCF7 and 293 cells. CARD-truncation mutants were unable to induce
cell death or activate NF-kappa B, whereas mutants with C-terminal truncat
ions retained NF-kappa B activation but did not induce apoptosis, Mutant BC
L10 overexpression might have a twofold lymphomagenic effect: loss of BCL10
pro-apoptosis may confer a survival advantage to MALT B-cells, and constit
utive NF-kappa B activation may provide both anti-apoptotic and proliferati
ve signals mediated via its transcriptional targets.