Molecular characterization of the genomic breakpoint junction in the t(11;18) (q21;q21) translocation of a gastric MALT lymphoma

The t(11;18) translocation, fusing the API2 and MALT1 genes, is one of the most frequent chromosomal translocations associated with mucos-aassociated lymphoid tissue (MALT) lymphomas. The translocation breakpoints have been cloned and characterized at the mRNA sequence level. Although the genomic organization of the API2 gene has been described, hitherto the genomic sequence of MALT1 remains unknown. To gain some insight into the mechanism that generates this translocation, we cloned and sequenced an API2-MALT1 fused transcript as well as genomic DNA of the t(11;18) translocation from a MALT lymphoma. We localized the API2 breakpoint within intron 7. Nucleotide sequence analysis revealed that the genomic breakpoint junction possesses the consensus heptamers of immunoglobulin V(D)J recombination signal sequences, all the matches being completely present on the API2 allele and five of seven matches on the MALT1 allele. These data suggest that the translocation in the MALT lymphoma might have been mediated in part by an aberrant V(D)J recombination event. (C) 2001 Academic Press.