title: TP53 mutations are frequent events in double-hit B-cell lymphomas with MYC and BCL2 but not MYC and BCL6 translocations.
abstract: Double-hit lymphomas (DHL) with MYC and either BCL2 or BCL6 rearrangements are rare neoplasms with an aggressive clinical presentation and grim prognosis. Moreover, molecular characterization of DHL remains insufficient, and especially the role of TP53 pathway disruption is unknown. We employed a next-generation sequencing approach to investigate the mutational status of TP53 in DHL and correlated genomic data with immunohistochemical reactivity for p53. We identified TP53 mutations in MYC+/BCL2+ lymphomas at a frequency intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma. Remarkably, TP53 mutations were particularly scarce in MYC+/BCL6+ lymphomas. Our findings indicate a significant difference between these two types of DHL at a molecular level with pathogenetic implications, as arguably, TP53 mutations inhibiting p53 mediated promotion of apoptosis pose a synergistic advantage in clonal evolution of cells with malignantly enforced overexpression of BCL2. Immunohistochemical staining appears to be a sensitive surrogate of TP53 mutation status with moderate specificity.
authors.affiliation: Department of Pathology, Reference Center for Lymph Node Pathology and Hematopathology, University Hospital of Schleswig-Holstein , Luebeck , Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Gebauer
authors.forename: Veronica
authors.initials: V
authors.lastname: Bernard
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Gebauer
authors.forename: Christoph
authors.initials: C
authors.lastname: Thorns
authors.forename: Alfred C
authors.initials: AC
authors.lastname: Feller
authors.forename: Hartmut
authors.initials: H
authors.lastname: Merz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D016259:Genes, myc; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6; D014178:Translocation, Genetic
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6
keywords: BCL2; BCL6; Double-hit lymphomas; TP53; cMYC