title: B cells in chronically hepatitis C virus-infected individuals lack a virus-induced mutation signature in the TP53, CTNNB1, and BCL6 genes.
abstract: Hepatitis C virus (HCV) is considered to have a causative role in B-cell lymphoproliferative diseases, including B-cell lymphomas, in chronic virus carriers. Previous data from in vitro HCV-infected B-cell lines and peripheral blood mononuclear cells from HCV-positive individuals suggested that HCV might have a direct mutagenic effect on B cells, inducing mutations in the tumor suppressor gene TP53 and the proto-oncogenes BCL6 and CTNNB1 (β-catenin). To clarify whether HCV indeed has a mutagenic effect on B cells in vivo, we analyzed naive and memory B cells from the peripheral blood of four chronic HCV carriers and intrahepatic B cells from the livers of two HCV-positive patients for mutations in the three reported target genes. However, no mutations were found in the TP53 and CTNNB1 genes. For BCL6, which is a physiological target of the somatic hypermutation process in germinal-center B cells, the mutation levels identified were not higher than those reported in the respective B-cell subsets in healthy individuals. Hence, we conclude that in chronic HCV carriers, the virus does not generally induce mutations in the cancer-related genes TP53, CTNNB1, and BCL6 in B cells. Based on these findings, new targets have to be investigated as potential mediators of HCV-associated B-cell lymphomagenesis.
authors.affiliation: Institute of Cell Biology (Cancer Research), University of Duisburg-Essen Medical School, Essen, Germany.
authors.forename: Felicia Anna
authors.initials: FA
authors.lastname: Tucci
authors.forename: Ruth
authors.initials: R
authors.lastname: Broering
authors.forename: Patricia
authors.initials: P
authors.lastname: Johansson
authors.forename: Joerg F
authors.initials: JF
authors.lastname: Schlaak
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
mesh_terms: D001402:B-Lymphocytes / Q000821:virology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D016174:Hepacivirus / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D006801:Humans; D008099:Liver / Q000276:immunology / Q000821:virology; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000821:virology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D051560:Proto-Oncogene Proteins c-bcl-6; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics*
chemical_list: C084103:BCL6 protein, human; C495270:CTNNB1 protein, human; D004268:DNA-Binding Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin