Distinct comparative genomic hybridisation profiles in gastric mucosa‐associated lymphoid tissue lymphomas with and without t(11;18)(q21;q21)

Abstract

T(11;18)(q21;q21) occurs specifically in mucosa‐associated lymphoid tissue (MALT) lymphoma and the translocation generates a functional API2‐MALT1 fusion product that activates nuclear factor (NF)κB. t(11;18) positive lymphomas usually lack the chromosomal aberrations and microsatellite alterations frequently seen in the translocation‐negative MALT lymphomas. To further understand their genetic differences, we investigated gastric MALT lymphomas with and without t(11;18) by comparative genomic hybridisation. In general, both chromosomal gains and losses were far more frequent in t(11;18)‐negative (median = 3·4 imbalances) than t(11;18)‐positive cases (median = 1·6 imbalances), with gains being more frequent than losses. Recurrent chromosomal gains involving whole or major parts of a chromosome were seen for chromosomes 3, 12, 18 and 22 (23%, 19%, 19% and 27% respectively). Discrete recurrent chromosomal gains were found at 9q34 (11/26 = 42%). Bioinformatic analysis of genes mapping to 9q34 revealed potential targets. Among them, TRAF2 and CARD9 are known interaction partners of BCL10, playing a role in NFκB activation. Interphase fluorescent in situ hybridisation confirmed genomic gain of the TRAF2, CARD9 and MALT1 loci in 5/6 and 2/2 cases showing chromosomal gains at 9q34 and 18q21 respectively. The results further highlight the genetic difference between MALT lymphomas with and without t(11;18). Moreover, our findings suggest that genomic gain of genes that modulate NFκB activation, such as MALT1, TRAF2 and CARD9, may play a role in the pathogenesis of the translocation‐negative MALT lymphoma.