title: Somatic hypermutation and mRNA expression levels of the BCL-6 gene in patients with hepatitis C virus-associated lymphoproliferative diseases.
abstract: Chronic hepatitis C virus (HCV) infection leads to mixed cryoglobulinaemia (MC) and B-cell non-Hodgkin lymphoma (B-NHL). Aberrant somatic hypermutation and deregulation of the oncogene BCL-6 is associated with lymphomagenesis. Recently, HCV was shown to induce BCL-6 mutations in vitro. The BCL-6 gene (area B) was cloned and sequenced from peripheral blood mononuclear cells (PBMC) of 21 chronically HCV-infected patients with or without MC and B-NHL, and six healthy controls. Mutational frequencies, genetic complexity and diversity were calculated. BCL-6 mRNA from PBMC was quantified by real-time polymerase chain reaction, and additional sustained virologic responders to antiviral therapy and HBV patients served as controls. The overall/recurrent mutational frequencies tended to be lower in MC and B-NHL patients when compared with controls (P = 0.15 and 0.06, respectively). Genetic complexity was significantly lower in MC and B-NHL patients (P = 0.025). BCL-6 mRNA concentration was decreased in all HCV patients when compared with healthy controls, sustained virologic responder and HBV patients (P = 0.005). Although HCV can induce BCL-6 mutations in vitro, lower mutational frequencies and decreased BCL-6 mRNA expression in vivo suggest no major role of aberrant somatic hypermutation in HCV-associated MC and B-NHL.
authors.affiliation: Klinik für Innere Medizin II, Kirrbergerstrasse, Universitätsklinikum des Saarlandes, Homburg, Germany.
authors.forename: W P
authors.initials: WP
authors.lastname: Hofmann
authors.forename: B
authors.initials: B
authors.lastname: Fernandez
authors.forename: E
authors.initials: E
authors.lastname: Herrmann
authors.forename: C
authors.initials: C
authors.lastname: Welsch
authors.forename: U
authors.initials: U
authors.lastname: Mihm
authors.forename: B
authors.initials: B
authors.lastname: Kronenberger
authors.forename: G
authors.initials: G
authors.lastname: Feldmann
authors.forename: U
authors.initials: U
authors.lastname: Spengler
authors.forename: S
authors.initials: S
authors.lastname: Zeuzem
authors.forename: C
authors.initials: C
authors.lastname: Sarrazin
mesh_terms: D001483:Base Sequence; D016384:Consensus Sequence; D003449:Cryoglobulinemia / Q000150:complications; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016174:Hepacivirus / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000150:complications; D008232:Lymphoproliferative Disorders / Q000150:complications*; D008969:Molecular Sequence Data; D009154:Mutation; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger