BCL10 gene mutation in lymphoma

BCL10 is directly involved in t(1;14)(p22; q32) of mucosa-associated lympho id tissue (MALT) lymphoma. Wild-type BCL10 promoted apoptosis and suppresse d malignant transformation in vitro, whereas truncated mutants lost the pro -apoptotic activity and exhibited gain of function enhancement of transform ation. We studied 220 lymphomas for genomic BCL10 mutation by polymerase ch ain reaction-single-strand conformational polymorphism and DNA sequencing. Nineteen mutations were found in 13 lymphoma specimens, as follows: 8 of 12 0 (6.7%) mucosa-associated lymphoid tissue (MALT) lymphomas, 4 of 42 (9.5%) follcular lymphomas, and 1 of 23 (4.3%) diffuse large B-cell lymphomas, No mutations were found in 14 mantle cell lymphomas or 21 T-cell lymphomas, H igh-grade MALT lymphoma tended to show a slightly higher mutation frequency (2 of 25, 8%) than low-grade MALT tumor (6 of 95, 6.3%), Among low-grade g astric MALT lymphoma, mutations were found in 3 of 11 tumors that did not r espond to Helicobacter pylori eradication therapy, but none were found in 2 2 tumors that regressed completely after H pylori eradication, All 14 poten tially pathogenic mutations were distributed in the carboxyl terminal domai n of BCL10. Deletion accounted for 10 of these mutations; 10 of 14 mutation s caused truncated forms of BCL10, Western blot analysis of a mutant case c onfirmed the presence of truncated BCL10 products of anticipated size. Our results suggest that BCL10 mutation may play a pathogenic role in B-cell ly mphoma development, particularly in aggressive and antibiotic unresponsive MALT lymphomas, and may further implicate the biologic importance of the ca rboxyl terminal of the molecule. (C) 2000 by The American Society ct Hemato logy.