title: 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)kappaB. 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 NFkappaB 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 NFkappaB activation, such as MALT1, TRAF2 and CARD9, may play a role in the pathogenesis of the translocation-negative MALT lymphoma.
authors.affiliation: Division of Molecular Histopathology, Department of Pathology, University of Cambridge, UK.
authors.forename: Yuanping
authors.initials: Y
authors.lastname: Zhou
authors.forename: Hongtao
authors.initials: H
authors.lastname: Ye
authors.forename: Jose I
authors.initials: JI
authors.lastname: Martin-Subero
authors.forename: Rifat
authors.initials: R
authors.lastname: Hamoudi
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Lu
authors.forename: Rubin
authors.initials: R
authors.lastname: Wang
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Janet
authors.initials: J
authors.lastname: Shipley
authors.forename: Peter G
authors.initials: PG
authors.lastname: Isaacson
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dogan
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Du
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D053468:CARD Signaling Adaptor Proteins; D020169:Caspases; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002887:Chromosomes, Human, Pair 18; D019295:Computational Biology; D005753:Gastric Mucosa / Q000473:pathology; D023281:Genomics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics* / Q000473:pathology; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D012815:Signal Processing, Computer-Assisted; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D047992:TNF Receptor-Associated Factor 2 / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D053468:CARD Signaling Adaptor Proteins; C505855:CARD9 protein, human; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D047992:TNF Receptor-Associated Factor 2; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein