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Blood, Vol. 95 No. 12 (June 15), 2000:
pp. 3885-3890
BCL10 gene mutation in lymphoma
Ming-Qing Du,
Huaizheng Peng,
Hongxiang Liu,
Rifat A. Hamoudi,
Tim C. Diss,
Tony G. Willis,
Hongtao Ye,
Ahmet Dogan,
Andrew
C. Wotherspoon,
Martin J. S. Dyer, and
Peter G. Isaacson
From the Department of Histopathology, Royal Free and
University College London Medical School, London; the Academic
Department of Haematology and Cytogenetics, Cancer Gene Cloning Center,
Institute of Cancer Research, Sutton; and the Department of
Histopathology, The Royal Marsden NHS Trust, London, United Kingdom.
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.
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