title: MALT lymphoma with t(14;18)(q32;q21)/IGH-MALT1 is characterized by strong cytoplasmic MALT1 and BCL10 expression.
abstract: Mucosa-associated lymphoid tissue (MALT) lymphoma is specifically associated with t(11;18)(q21;q21), t(1;14)(p22;q32) and t(14;18)(q32;q21). t(11;18)(q21;q21) fuses the N-terminus of the API2 gene to the C-terminus of the MALT1 gene and generates a functional API2-MALT1 product. t(1;14)(p22;q32) and t(14;18)(q32;q21) bring the BCL10 and MALT1 genes respectively to the IGH locus and deregulate their expression. The oncogenic activity of the three chromosomal translocations is linked by the physiological role of BCL10 and MALT1 in antigen receptor-mediated NFkappaB activation. In this study, MALT1 and BCL10 expression was examined in normal lymphoid tissues and 423 cases of MALT lymphoma from eight sites, and their expression was correlated with the above translocations, which were detected by molecular and molecular cytogenetic methods. In normal B-cell follicles, both MALT1 and BCL10 were expressed predominantly in the cytoplasm, high in centroblasts, moderate in centrocytes and weak/negative in mantle zone B-cells. In MALT lymphoma, MALT1 and BCL10 expression varied among cases with different chromosomal translocations. In 9/9 MALT lymphomas with t(14;18)(q32;q21), tumour cells showed strong homogeneous cytoplasmic expression of both MALT1 and BCL10. In 12/12 cases with evidence of t(1;14)(p22;q32) or variants, tumour cells expressed MALT1 weakly in the cytoplasm but BCL10 strongly in the nuclei. In all 67 MALT lymphomas with t(11;18)(q21;q21), tumour cells expressed weak cytoplasmic MALT1 and moderate nuclear BCL10. In MALT lymphomas without the above translocations, both MALT1 and BCL10, in general, were expressed weakly in the cytoplasm. Real-time quantitative RT-PCR showed a good correlation between MALT1 and BCL10 mRNA expression and underlining genetic changes, with t(14;18)(q32;q21)- and t(1;14)(p22;q32)-positive cases displaying the highest MALT1 and BCL10 mRNA expression respectively. These results show that MALT1 expression pattern is identical to that of BCL10 in normal lymphoid tissues but varies in MALT lymphomas, with high cytoplasmic expression of both MALT1 and BCL10 characterizing those with t(14;18)(q32;q21).
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, UK.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Ye
authors.forename: Liping
authors.initials: L
authors.lastname: Gong
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Liu
authors.forename: Rifat A
authors.initials: RA
authors.lastname: Hamoudi
authors.forename: Sima
authors.initials: S
authors.lastname: Shirali
authors.forename: Liza
authors.initials: L
authors.lastname: Ho
authors.forename: Andreas
authors.initials: A
authors.lastname: Chott
authors.forename: Berthold
authors.initials: B
authors.lastname: Streubel
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Stefan
authors.initials: S
authors.lastname: Gesk
authors.forename: Jose I
authors.initials: JI
authors.lastname: Martin-Subero
authors.forename: John A
authors.initials: JA
authors.lastname: Radford
authors.forename: Sankar
authors.initials: S
authors.lastname: Banerjee
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Nicholson
authors.forename: Renzo
authors.initials: R
authors.lastname: Ranaldi
authors.forename: Ellen D
authors.initials: ED
authors.lastname: Remstein
authors.forename: Zifen
authors.initials: Z
authors.lastname: Gao
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
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 / Q000378:metabolism; D000074018:B-Cell CLL-Lymphoma 10 Protein; D020169:Caspases; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D008221:Lymphoid Tissue / Q000378:metabolism; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics* / Q000378:metabolism; D008297:Male; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014178:Translocation, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein