title: Primary cutaneous marginal zone B-cell lymphomas are targeted by aberrant somatic hypermutation.
abstract: A mechanism inducing genetic instability, termed aberrant somatic hypermutation (ASHM), has been described in diffuse large B-cell lymphoma. To further investigate whether ASHM also occurs in primary cutaneous marginal zone B-cell lymphoma (PCMZL), we studied the mutational profile of PAX5, RhoH/TTF, cMYC, and PIM1 in 11 PCMZLs. A total of 17 sequence variants were found in 8 of 11 lymphomas cases (72.7%), and they displayed the molecular features typical for the ASHM. Further, two mutations, one mutation in PIM1 and one in cMYC, led to amino-acid substitution with potential functional consequences. These data indicate that ASHM is associated with PCMZLs. By mutating regulatory and coding sequences of the targeted genes, ASHM may represent a major contributor to their pathogenesis.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Medical University Graz, Graz, Austria.
authors.forename: Alexander J A
authors.initials: AJ
authors.lastname: Deutsch
authors.forename: Margareta
authors.initials: M
authors.lastname: Frühwirth
authors.forename: Ariane
authors.initials: A
authors.lastname: Aigelsreiter
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cerroni
authors.forename: Peter
authors.initials: P
authors.lastname: Neumeister
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D004252:DNA Mutational Analysis; D042822:Genomic Instability; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics*; D051757:PAX5 Transcription Factor / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D051573:Proto-Oncogene Proteins c-pim-1 / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics*; D027041:Somatic Hypermutation, Immunoglobulin; D014157:Transcription Factors / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000235:genetics
chemical_list: C489427:MYC protein, human; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D016271:Proto-Oncogene Proteins c-myc; C447841:RhoH protein, human; D014157:Transcription Factors; C496634:PIM1 protein, human; D051573:Proto-Oncogene Proteins c-pim-1; D020741:rho GTP-Binding Proteins