Abstract: |
Low-grade B cell lymphomas of mucosa-associated lymphoid tissue (MALT) represent a distinct clinicopathological entity that arises in a wide variety of extranodal sites. Genetically, MALT lymphomas are characterized by the t(11;18)(q21;q21). The genes involved in this translocation have been identified to be API2 on chromosome 11, which encodes an apoptotic inhibitor, and MALT1, a novel gene on chromosome 18. We identified the t(11;18)(q21;q21) by Southern blot analysis and reverse transcriptase PCR in 42% of a panel of extranodal MALT lymphomas. We also identified the breakpoints within the API2 and MALT1 genes in 7 patients, which revealed a consistent breakpoint after the third baculoviral inhibitor of apoptosis repeat domain within API2, and variable breakpoints in MALT1. We determined the API2/MALT1 fusion transcript in 2 cases by Northern blot analysis and also showed that MALT1 mRNA is constitutively expressed in a variety of human tissues. To understand the functional consequence of the translocation, we determined the pattern of expression of API2 and MALT1 through B lineage differentiation. API2 was expressed only in cell lines which correspond to mature B cells, whereas MALT1 mRNA was detectable in pre-B cells, mature B cells and plasma cells. These results suggest that fusion of MALT1 to API2 mediated by the t(11;18)(q21;q21) may result in an increased inhibition of germinal center B cell apoptosis and subsequent development of MALT lymphomas. Copyright (C) 2000 S. Karger AG, Basel. |
Keywords: |
controlled study; human tissue; unclassified drug; human cell; proteins; apoptosis; gene expression; neoplasm proteins; cell protein; cell differentiation; caspases; carcinogenesis; b-lymphocytes; rna; b cell lymphoma; germinal center; hybrid protein; messenger rna; inhibitor of apoptosis proteins; gene fusion; oncogene proteins, fusion; translocation, genetic; sequence analysis, rna; blotting, northern; b lymphocyte differentiation; chromosome translocation 11; mucosa associated lymphoid tissue lymphoma; baculovirus; mucosa-associated lymphoid tissue; blotting, southern; lymphoma, mucosa-associated lymphoid tissue; humans; human; article; chromosome translocation 18; api2/malt1 fusion; protein api2; protein malt1
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