| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1998: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
In a recent year, much interest is focused on the biologic behavior of extranodal lymphomas, especially of mucosa-associated lymphoid tissue (MALT) type. The t(11;18)(q21;q21) translocation is a characteristic chromosomal aberration in low-grade B-cell lymphoma of MALT type. We have 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. 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 BAC193f9. The breakpoints at 18q21 in three of the five MALT lymphoma patients were found to be clustered approximately within the 20kb 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 refereed to the gene encoding this transcript as MALT1. The alteration of MALT1 by translocation strongly suggested that this gene plays an important role in the pathogenesis of MALT lymphoma. Notably, among them, MALT lymphoma with API2-MALT1 gene expression appeared to constitute a homogeneous disease entity. The microscopic appearance is distinctive enough for the diagnosis to be made or at least entertained in routine sections. Their anatomical sites also preferred to lung, intestine, and less commonly stomach. In addition, gastric MALT lymphoma with the genetic alteration of API2-MALT1 seemed to have no relationship with Helicobacter pylori infection. The presence of this set of features in this distinctive tumors has not been sufficiently emphasized in previous reports.
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