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
Murga Penas, Eva Maria × Callet-Bauchu, Evelyne Ye, Hongtao Gazzo, Sophie Berger, Francoise Schilling, Georgia Albert-Konetzny, Nadine Vettorazzi, Eik Salles, Gilles Wlodarska, Iwona Du, Ming-Qing Bokemeyer, Carsten Dierlamm, Judith #
Blood vol:115 issue:11 pages:2214-2219
The t(14;18)(q32;q21) involving the immunoglobulin heavy chain locus (IGH) and the MALT1 gene is a recurrent abnormality in 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 (RSS)-guided V(D)J-mediated translocation at the IGH locus. Furthermore, analogous to follicular and mantle cell lymphoma, templated T-nucleotides were identified at the t(14;18)/IGH-MALT1 breakpoint junctions. On chromosome 18, we identified a novel major breakpoint region (MBR) 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 FL and t(11;14)/CCND1-IGH in MCL suggesting that these translocations could be generated by common pathomechanisms involving illegitime V(D)J-mediated recombination on IGH as well as new synthesis of T-nucleotides and non-homologous end joining (NHEJ) or alternative NHEJ repair pathways on the IGH-translocation partner.