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

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.

Mutual exclusion of t(11;18)(q21;q21) and numerical chromosomal aberrations in the development of different types of primary gastric lymphomas

“…In addition to the detection of t(11;18)(q21;q21), FISH can be used to detect additional aberrations in the breakpoint regions involved (Baens et al, 2000b;Dierlamm et al, 2000) or other translocations involving 11q21 and 18q21 and other partner chromosomes (Streubel et al, 2003). Dierlamm et al (1999Dierlamm et al ( , 2000 showed a cryptic deletion of chromosome 11 sequences distal to the breakpoint in one case. We did not detect this deletion in eight t(11;18)(q21;q21)-positive cases, using the same API2-specific PAC probe.…”

G‐banding and molecular cytogenetic analyses of marginal zone lymphoma

“…The most characteristic structural chromosomal rearrangement in MZL has been the t(11;18)(q21;q21) reported in up to 50% of extranodal MZL (Auer et al, 1997;Ott et al, 1997). It involves the apoptosis inhibitor-2 (API2) gene in 11q21 and the mucosa-associated lymphoid tissue (MALT) lymphoma-associated translocation gene (MALT1) in 18q21 (Dierlamm et al, 1999). We found this translocation in only one extranodal MZL, where it was the sole abnormality (case 4).…”

Genetic and epigenetic factors involved in B‐cell lymphomagenesis

“…27) API2-MALT1 chimeric products were identified as a result of the analysis of t(11;18)(q21;q21). [28][29][30] MALT1 is a novel protein with unknown function. 28,29) BCL10 was isolated from the chromosome translocation junction region at 1p22 that is activated by juxtaposition of the IgH gene in t(1;14)(p22;q34).…”

“…[28][29][30] MALT1 is a novel protein with unknown function. 28,29) BCL10 was isolated from the chromosome translocation junction region at 1p22 that is activated by juxtaposition of the IgH gene in t(1;14)(p22;q34). 22) It was recently found that MALT1 and BCL10 play an important role in signal transduction of cellsurface antigen receptors on B and T lymphocytes.…”

“…4). 22,[27][28][29][30] H. pylori gastritis inflammation also plays a major role in gastric MALT lymphomagenesis. Although the kinetics differ, both API2 and MALT1 in lymphoid cells are transcriptionally activated upon PHA stimulation, suggesting that both genes are upregulated under inflammatory conditions (Fig.…”