title: 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.
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.
authors: Department of Oncology and Hematology, BMT with Section of Pneumology, Hubertus Wald Tumorzentrum-University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. murga@uke.unihamburg.de
authors: Eva Maria
authors: EM
authors: Murga Penas
authors: Evelyne
authors: E
authors: Callet-Bauchu
authors: Hongtao
authors: H
authors: Ye
authors: Sophie
authors: S
authors: Gazzo
authors: Françoise
authors: F
authors: Berger
authors: Georgia
authors: G
authors: Schilling
authors: Nadine
authors: N
authors: Albert-Konetzny
authors: Eik
authors: E
authors: Vettorazzi
authors: Gilles
authors: G
authors: Salles
authors: Iwona
authors: I
authors: Wlodarska
authors: Ming-Qing
authors: MQ
authors: Du
authors: Carsten
authors: C
authors: Bokemeyer
authors: Judith
authors: J
authors: Dierlamm
mesh_terms: D000368:Aged; D001483:Base Sequence; D020169:Caspases / Q000235:genetics*; D056905:Chromosome Breakpoints; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics*; D008224:Lymphoma, Follicular / Q000235:genetics; D020522:Lymphoma, Mantle-Cell / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D016254:Mutagenesis, Insertional / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D009711:Nucleotides / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D013698:Templates, Genetic; D014178:Translocation, Genetic
chemical_list: C548564:IGH-MALT1 fusion protein, human; D007143:Immunoglobulin Heavy Chains; D009363:Neoplasm Proteins; D009711:Nucleotides; D015514:Oncogene Proteins, Fusion; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein