The t(14;18)(q32;q21)/IGH-MALT1 translocation in MALT lymphomas contains templated nucleotide insertions and a major breakpoint region similar to follicular and mantle cell lymphoma

Blood. 2010 Mar 18;115(11):2214-9. doi: 10.1182/blood-2009-08-236265. Epub 2009 Nov 25.

Abstract

The t(14;18)(q32;q21) involving the immunoglobulin heavy chain locus (IGH) and the MALT1 gene is a recurrent abnormality in mucosa-associated lymphoid tissue (MALT) lymphomas. However, the nucleotide sequence of only one t(14;18)-positive MALT lymphoma has been reported so far. We here report the molecular characterization of the IGH-MALT1 fusion products in 5 new cases of t(14;18)-positive MALT lymphomas. Similar to the IGH-associated translocations in follicular and mantle cell lymphomas, the IGH-MALT1 junctions in MALT lymphoma showed all features of a recombination signal sequence-guided V(D)J-mediated translocation at the IGH locus. Furthermore, analogous to follicular and mantle cell lymphoma, templated nucleotides (T-nucleotides) were identified at the t(14;18)/IGH-MALT1 breakpoint junctions. On chromosome 18, we identified a novel major breakpoint region in MALT1 upstream of its coding region. Moreover, the presence of duplications of MALT1 nucleotides in one case suggests an underlying staggered DNA-break process not consistent with V(D)J-mediated recombination. The molecular characteristics of the t(14;18)/IGH-MALT1 resemble those found in the t(14;18)/IGH-BCL2 in follicular lymphoma and t(11;14)/CCND1-IGH in mantle cell lymphoma, suggesting that these translocations could be generated by common pathomechanisms involving illegitimate V(D)J-mediated recombination on IGH as well as new synthesis of T-nucleotides and nonhomologous end joining (NHEJ) or alternative NHEJ repair pathways on the IGH-translocation partner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Base Sequence
  • Caspases / genetics*
  • Chromosome Breakpoints*
  • Chromosomes, Human, Pair 14 / genetics*
  • Chromosomes, Human, Pair 18 / genetics*
  • Female
  • Genetic Loci / genetics
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Lymphoma, B-Cell, Marginal Zone / genetics*
  • Lymphoma, Follicular / genetics
  • Lymphoma, Mantle-Cell / genetics
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
  • Mutagenesis, Insertional / genetics*
  • Mutation / genetics
  • Neoplasm Proteins / genetics*
  • Nucleotides / genetics
  • Oncogene Proteins, Fusion / genetics*
  • Templates, Genetic
  • Translocation, Genetic*

Substances

  • IGH-MALT1 fusion protein, human
  • Immunoglobulin Heavy Chains
  • Neoplasm Proteins
  • Nucleotides
  • Oncogene Proteins, Fusion
  • Caspases
  • MALT1 protein, human
  • Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein