BCL10 gene mutation in lymphoma.
BCL10 is directly involved in t(1;14)(p22;q32) of mucosa-associated lymphoid tissue (MALT) lymphoma. Wild-type BCL10 promoted apoptosis and suppressed malignant transformation in vitro, whereas truncated mutants lost the pro-apoptotic activity and exhibited gain of function enhancement of transformation. We studied 220 lymphomas for genomic BCL10 mutation by polymerase chain reaction-single-strand conformational polymorphism and DNA sequencing. Nineteen mutations were found in 13 lymphoma specimens, as follows: 8 of 120 (6.7%) mucosa-associated lymphoid tissue (MALT) lymphomas, 4 of 42 (9.5%) follicular 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. High-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 gastric MALT lymphoma, mutations were found in 3 of 11 tumors that did not respond to Helicobacter pylori eradication therapy, but none were found in 22 tumors that regressed completely after H pylori eradication. All 14 potentially pathogenic mutations were distributed in the carboxyl terminal domain of BCL10. Deletion accounted for 10 of these mutations; 10 of 14 mutations caused truncated forms of BCL10. Western blot analysis of a mutant case confirmed the presence of truncated BCL10 products of anticipated size. Our results suggest that BCL10 mutation may play a pathogenic role in B-cell lymphoma development, particularly in aggressive and antibiotic unresponsive MALT lymphomas, and may further implicate the biologic importance of the carboxyl terminal of the molecule. (Blood. 2000;95:3885-3890)
Du
M Q
MQ
Department of Histopathology, Royal Free and University College London Medical School, London, United Kingdom. m.du@ucl.ac.uk
Peng
H
H
Liu
H
H
Hamoudi
R A
RA
Diss
T C
TC
Willis
T G
TG
Ye
H
H
Dogan
A
A
Wotherspoon
A C
AC
Dyer
M J
MJ
Isaacson
P G
PG
D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D000074018:B-Cell CLL-Lymphoma 10 Protein; D001483:Base Sequence; D005091:Exons; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000473:pathology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics* / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012189:Retrospective Studies; D017384:Sequence Deletion
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D009363:Neoplasm Proteins