ArticleProceedings of the National Academy of Sciences of the United States of America2004
Hepatitis C virus induces a mutator phenotype: enhanced mutations of immunoglobulin and protooncogenes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 156 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
156 citing papers in PubMed, 2 syntheses or guidelines pooled it, 378 citations in OpenAlex.
- Hepatitis B and C virus infection and risk of multiple myeloma: a systematic review and meta-analysis.BMC cancer · 2025Pooled it
- Hepatitis C infection and lymphoproliferative disease: accidental comorbidities?World journal of gastroenterology · 2014Pooled it
- Predictive Value of Cytokines and Immune Activation Biomarkers in AIDS-Related Non-Hodgkin Lymphoma Treated with Rituximab plus Infusional EPOCH (AMC-034 trial).Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Trial
- A role for host activation-induced cytidine deaminase in innate immune defense against KSHV.PLoS pathogens · 2013Trial
- From Antigenic Drive to Clonal Autonomy: An Update on Molecular Mechanisms of HCV-Related B-Cell Lymphomagenesis.Cancers · 2026Review
- Cryoglobulinemia: An update on classification, pathophysiology, clinical presentation, and management.Journal of internal medicine · 2026Review
- Mechanisms and Therapeutic Strategies for HCV/HBV-Associated B-Cell Non-Hodgkin's Lymphomas: A Viewpoint.Oncology research · 2026Review
- Hepatitis C virus-associated B-cell non-Hodgkin lymphomas: immune evasion, multistep lymphomagenesis, and candidate biomarkers for risk stratification and disease monitoring.Frontiers in immunology · 2026Review
- B Cell Differentiation and the Origin and Pathogenesis of Human B Cell Lymphomas.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Extrahepatic Cancer Risk in Patients with Hepatitis C Virus Infection Treated with Direct-Acting Antivirals.Microorganisms · 2024Review
- Leveraging oncovirus-derived antigen against the viral malignancies in adoptive cell therapies.Biomarker research · 2024Review
- Carcinogenic mechanisms of virus-associated lymphoma.Frontiers in immunology · 2024Review
- High prevalence of past hepatitis B virus infection in diffuse large B cell lymphoma: a retrospective study from Italy.Annals of hematology · 2023Article
- SARS-CoV-2 and the DNA damage response.The Journal of general virology · 2023Review
- Hepatitis Virus-associated Non-hodgkin Lymphoma: Pathogenesis and Treatment Strategies.Journal of clinical and translational hepatology · 2023Review
- Associations of Head and Neck Cancer with Hepatitis B Virus and Hepatitis C Virus Infection.Cancers · 2023Article
- Hepatitis C Virus (HCV)-Ribonucleic Acid (RNA) As a Biomarker for Lymphoid Malignancy with HCV Infection.Cancers · 2023Review
- Neoplastic and Autoimmune Comorbidities in Patients with Primary Cutaneous B-Cell Lymphoma.Hematology reports · 2023Article
- Review
- Viral Encoded miRNAs in Tumorigenesis: Theranostic Opportunities in Precision Oncology.Microorganisms · 2022Review
96 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Hepatitis C virus (HCV) is a nonretroviral oncogenic RNA virus, which is frequently associated with hepatocellular carcinoma (HCC) and B cell lymphoma. We demonstrated here that acute and chronic HCV infection caused a 5- to 10-fold increase in mutation frequency in Ig heavy chain, BCL-6, p53, and beta-catenin genes of in vitro HCV-infected B cell lines and HCV-associated peripheral blood mononuclear cells, lymphomas, and HCCs. The nucleotide-substitution pattern of p53 and beta-catenin was different from that of Ig heavy chain in HCV-infected cells, suggesting two different mechanisms of mutation. In addition, the mutated protooncogenes were amplified in HCV-associated lymphomas and HCCs, but not in lymphomas of nonviral origin or HBV-associated HCC. HCV induced error-prone DNA polymerase zeta, polymerase iota, and activation-induced cytidine deaminase, which together, contributed to the enhancement of mutation frequency, as demonstrated by the RNA interference experiments. These results indicate that HCV induces a mutator phenotype and may transform cells by a hit-and-run mechanism. This finding provides a mechanism of oncogenesis for an RNA virus.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.