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A novel gene, MALT1 at 18q21, is involved in t(11;18) (q21;q21) found in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue

Abstract

The t(11;18) (q21;q21) translocation is a characteristic chromosomal aberration in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. We previously identified a YAC clone y789F3, which includes the breakpoint at 18q21 in a MALT lymphoma patient. BAC and PAC contigs were constructed on the YAC, and BAC 193f9 was found to encompass the breakpoint region. In the present study, we further narrowed down the breakpoint region at 18q21 in five MALT lymphoma patients by means of FISH and Southern blot analyses using the plasmid contig constructed from BAC 193f9. The breakpoints at 18q21 in three of the five MALT lymphoma patients were found to be clustered approximately within the 20 kb region. By using exon amplification and cDNA library screening, we identified a novel cDNA spanning the breakpoint region that exhibited aberrant mRNA signals in four of the five MALT lymphoma patients. The nucleotide sequence predicted an 813 amino acid protein that shows significant sequence similarity to the CD22β and laminin 5 α3b subunit. We refer to the gene encoding this transcript as MALT1 (Mucosa-Associated Lymphoid Tissue lymphoma translocation gene 1). The alteration of MALT1 by translocation strongly suggests that this gene plays an important role in the pathogenesis of MALT lymphoma.

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Acknowledgements

We would like to thank Dr T Joh for his valuable discussions, and express our appreciation for the technical assistance of Mss T Kobayashi and Y Maeda. We also wish to thank Dr T Rabbitts for his valuable suggestions. Drs A Munakata and H Takami are appreciated for their encouragement and support throughout the study. This work was supported in part by a Grant-in-aid for the 2nd-Term Comprehensive 10-year Strategy for Cancer Control from the Ministry of Health and Welfare, a Grant-in-aid for Science on Primary Areas (Cancer Research), a Grant-in-aid for the Encouragement of Young Scientists from the Ministry of Education, Science and Culture, Japan, a Grant-in-aid from the Uehara Memorial Foundation, and the Bristol-Myers Squibb Unrestricted Biomedical Research Grants Program.

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Akagi, T., Motegi, M., Tamura, A. et al. A novel gene, MALT1 at 18q21, is involved in t(11;18) (q21;q21) found in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue. Oncogene 18, 5785–5794 (1999). https://doi.org/10.1038/sj.onc.1203018

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