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

Blood. 2003 Jun 1;101(11):4539-46. doi: 10.1182/blood-2002-10-3236. Epub 2003 Jan 30.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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
  • Lymphoma, B-Cell / genetics*
  • Lymphoma, B-Cell / pathology
  • Lymphoma, B-Cell, Marginal Zone / etiology
  • Lymphoma, B-Cell, Marginal Zone / genetics*
  • Lymphoma, B-Cell, Marginal Zone / pathology
  • Male
  • Middle Aged
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics*
  • RNA, Neoplasm / analysis
  • Translocation, Genetic*

Substances

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