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

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. Ofthe 3 cell lines with MALT1 amplification, 2 showed MALT1 overexpression as assessed by gene profiling, quantitative reverse transcription-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.

• Authors: 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
• Journal: Blood (Blood) Vol. 101 Issue 11 Pg. 4539-46 (Jun 01 2003) ISSN: 0006-4971 [Print] United States
• PMID: 12560219 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Neoplasm Proteins
• RNA, Neoplasm
• Caspases
• MALT1 protein, human
• Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein

Topics

• Aged
• Caspases
• Chromosomes, Human, Pair 14
• Chromosomes, Human, Pair 18
• Female
• Gene Amplification
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Genes, bcl-2
• Humans
• Lymphoma, B-Cell (etiology, genetics, pathology)
• Lymphoma, B-Cell, Marginal Zone (etiology, genetics, pathology)
• Male
• Middle Aged
• Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
• Neoplasm Proteins (biosynthesis, genetics)
• RNA, Neoplasm (analysis)
• Translocation, Genetic