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Blood ; 115(11): 2214-9, 2010 Mar 18.
Article in English | MEDLINE | ID: mdl-19965626

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.


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