The Apoptosis Inhibitor Gene API2 and a Novel 18q Gene,MLT, Are Recurrently Rearranged in the t(11;18)(q21;q21) Associated With Mucosa-Associated Lymphoid Tissue Lymphomas

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Abstract
Marginal zone cell lymphomas of the mucosa-associated lymphoid tissue (MALT) are the most common subtype of lymphoma arising at extranodal sites. The t(11;18)(q21;q21) appears to be the key genetic lesion and is found in approximately 50% of cytogenetically abnormal low-grade MALT lymphomas. We show that the API2 gene, encoding an inhibitor of apoptosis also known as c-IAP2, HIAP1, andMIHC, and a novel gene on 18q21 characterized by several Ig-like C2-type domains, named MLT, are recurrently rearranged in the t(11;18). In both MALT lymphomas analyzed, the breakpoint inAPI2 occurred in the intron separating the exons coding respectively for the baculovirus IAP repeat domains and the caspase recruitment domain. The breakpoints within MLT differed but the open reading frame was conserved in both cases. In one case, the translocation was accompanied by a cryptic deletion involving the 3′ part of API2. As a result, the reciprocal transcript was not present, strongly suggesting that the API2-MLT fusion is involved in the oncogenesis of MALT lymphoma.

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