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Somatic hypermutation and mRNA expression levels of the BCL‐6 gene in patients with hepatitis C virus‐associated lymphoproliferative diseases *
Author(s) -
Hofmann W. P.,
Fernandez B.,
Herrmann E.,
Welsch C.,
Mihm U.,
Kronenberger B.,
Feldmann G.,
Spengler U.,
Zeuzem S.,
Sarrazin C.
Publication year - 2007
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/j.1365-2893.2006.00833.x
Subject(s) - somatic hypermutation , peripheral blood mononuclear cell , hepatitis c virus , biology , immunology , virology , hepatitis b virus , somatic cell , b cell , virus , gene , cancer research , antibody , in vitro , genetics
Summary. 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.