title: MALT lymphoma and extranodal diffuse large B-cell lymphoma are targeted by aberrant somatic hypermutation.
abstract: Recently, a novel mechanism introducing genetic instability, termed aberrant somatic hypermutation (ASHM), has been described in diffuse large B-cell lymphoma. To further investigate whether ASHM also occurs in mucosa-associated lymphoid tissue type (MALT) lymphoma, we studied the mutation profile of PIM1, PAX5, RhoH/TTF, and c-MYC in 17 MALT lymphomas and 17 extranodal diffuse large B-cell lymphomas (DLBCLs) still exhibiting a low-grade MALT lymphoma component (transformed MALT lymphoma). Mutations in one or more genes were detected in 13 (76.5%) of 17 cases of MALT lymphomas and in all of 17 (100%) cases of extranodal DLBCL. A total of 100 sequence variants were found in 30 of 34 cases, 28 in the MALT lymphomas and 72 in extranodal DLBCL. Further, in PIM1 and c-MYC some of the mutations were found to affect coding exons, leading to amino acid exchanges, thus potentially altering gene function. Expression levels of activation-induced cytidine deaminase (AID), an enzyme essential for somatic hypermutation (SHM), was associated with the mutational load. These data indicate that aberrant SHM is associated with extranodal DLBCL and MALT lymphoma, likewise. By mutating regulatory and coding sequences of the targeted genes, ASHM may represent a major contributor to their pathogenesis.
authors.affiliation: Division of Haematology, Medical University Graz, Auenbruggerplatz 38, A-8036 Graz, Austria.
authors.forename: Alexander J A
authors.initials: AJ
authors.lastname: Deutsch
authors.forename: Ariane
authors.initials: A
authors.lastname: Aigelsreiter
authors.forename: Philipp B
authors.initials: PB
authors.lastname: Staber
authors.forename: Alfred
authors.initials: A
authors.lastname: Beham
authors.forename: Werner
authors.initials: W
authors.lastname: Linkesch
authors.forename: Christian
authors.initials: C
authors.lastname: Guelly
authors.forename: Ruth I
authors.initials: RI
authors.lastname: Brezinschek
authors.forename: Margareta
authors.initials: M
authors.lastname: Fruhwirth
authors.forename: Werner
authors.initials: W
authors.lastname: Emberger
authors.forename: Maike
authors.initials: M
authors.lastname: Buettner
authors.forename: Christine
authors.initials: C
authors.lastname: Beham-Schmid
authors.forename: Peter
authors.initials: P
authors.lastname: Neumeister
mesh_terms: D042822:Genomic Instability; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics
chemical_list: D009363:Neoplasm Proteins