MALT1 is deregulated by both chromosomal translocation and amplification in B-cell non-Hodgkin lymphoma

Dolors Sanchez-Izquierdo, Gerard Buchonnet, Reiner Siebert, Randy D. Gascoyne, Joan Climent, Loraine Karran, Miguel Marin, David Blesa, Douglas Horsman, Andreas Rosenwald, Louis M. Staudt, Donna G. Albertson, Ming Qing Du, Hongtao Ye, Peter Marynen, Javier Garcia-Conde, Daniel Pinkel, Martin J S Dyer, Jose Angel Martinez-Climent

Research output: Contribution to journalArticle

Abstract

The MALT1 gene was identified through its involvement in t(11;18)(q21;q21), seen in 30% of cases of mucosa-associated lymphoid tissue (MALT) lymphoma. Here, we show that deregulated MALT1 expression may occur in B-cell non-Hodgkin lymphoma (B-NHL) of various histologic subtypes either through translocation to the immunoglobulin heavy chain (IGH) locus or by genomic amplification. First, 2 cases, one case of MALT lymphoma and another of aggressive marginal zone lymphoma (MZL) with t(14;;18)(q32;q21), cytogenetically identical to the translocation involving BCL2, were shown by fluorescence in situ hybridization (FISH) to involve MALT1, which lies about 5 Mb centromeric of BCL2. Molecular cloning of both by long-distance inverse polymerase chain reaction showed breakpoints lying 1 to 2 kilobase (kb) centromeric of the first 5′ MALT1 exon; both cases showed MALT1 overexpression at either RNA or protein levels. Second, we examined the structure and gene expression profile of genomic amplifications involving 18q21 in a panel of 40 B-NHL cell lines using comparative genomic hybridization to microarrays (array CGH) and gene expression profiling techniques. Using array CGH, 2 peaks of genomic amplification were observed, one centered around BCL2 and the other around MALT1. Of the 3 cell lines with MALT1 amplification, 2 showed MALT1 overexpression as assessed by gene profiling, quantitative reverse trapscription-polymerase chain reaction (QRT-PCR), and Western blotting. To determine if comparable events occurred in primary MALT and splenic MZL tumors, 40 cases were analyzed by FISH or QRT-PCR; genomic amplification and MALT1 overexpression were seen in 2 cases. Together, these data implicate MALT1 as a dominant oncogene that may play a role in the pathogenesis of B-NHL.

Original languageEnglish (US)
Pages (from-to)4539-4546
Number of pages8
JournalBlood
Volume101
Issue number11
DOIs
StatePublished - Jun 1 2003

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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