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LYMPHOMA

Exploring the genetic landscape of HCV-related B-cell lymphomas using whole exome sequencing

Leukemia volume 37, pages 1388–1391 (2023)Cite this article

Subjects

Hepatitis C virus (HCV) infection has been found to be associated with extrahepatic immune manifestations such as mixed cryoglobulinemia (MC) and B-cell non-Hodgkin lymphoma (B-NHL), mostly marginal zone lymphoma (MZL), de novo or transformed diffuse large B-cell lymphoma (DLBCL) [1]. Two main pathways have been proposed to explain the role of the virus in lymphomagenesis: (1) chronic antigenic stimulation through the B cell receptor (BCR) leading from oligoclonal to monoclonal expansion and ultimately to overt lymphoma, mostly of marginal zone subtype or (2) transformation of B cells either directly by oncogenic viral proteins, or by a hit-and-run mechanism inducing a mutator phenotype, particularly in de novo large B-cell lymphoma [1]. In recent years, direct-acting antiviral agents (DAA) have demonstrated their efficacy to obtain sustained HCV eradication in chronic hepatitis C virus infection but also to induce remission in MC and indolent low-grade NHL. Thus, in this subset of patients, HCV treatment has been recommended as first-line therapy without chemotherapy [2]. Regarding high grade lymphoma, optimal management has yet to be determined and combination of DAA with chemotherapy is still under evaluation [3].

In this context, unraveling the molecular oncogenesis of HCV-related B-cell lymphoproliferations is essential to decipher their pathogenesis and to optimize therapeutic strategies. However, available molecular data of HCV-associated NHL are still limited so far and exclusively arise from targeted sequencing [4,5,6].

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Fig. 1: Pattern of somatic mutations in HCV-associated B-NHL.
Fig. 2: Landscape of somatic alterations in HCV-associated B-NHL.

Data availability

WES data have been deposited in the European Genome-phenome Archive (EGA) under accession EGAS00001006860.

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Acknowledgements

This work was supported by a grant from ANRS (Agence Nationale de Recherches sur le Sida et les Hépatites Virales) (reference number: ECTZ22779) and in part by an ERA-NET TRANSCAN-2/French National Cancer Institute grant (acronym NOVEL). We are grateful to the patients for their participation. We would also like to thank all the staff from the Imagine genomic core facility and the Cytometry facility CyPS (Plateforme de cytométrie CyPS, Pitié-Salpêtrière, Sorbonne Université, Paris) for their advice and excellent technical support. We acknowledge all the participating tumor biobanks for managing and providing biological samples: Saint-Louis Hospital, Centre de Ressources Biologiques-Cancer de Toulouse, Centre de Ressources Biologiques de Limoges (CRBioLim), Centre de Ressources Biologiques de la Tumorothèque de Rouen, Lyon Sud Hospital, Necker-Enfants malades Hospital, Pitié-Salpêtrière Hospital.

Author information

Author notes

  1. These authors contributed equally: Marine Armand, Michaël Degaud.

  2. These authors jointly supervised this work: Olivier Hermine, Frédéric Davi, Lucile Couronné.

Authors and Affiliations

  1. Hematology Laboratory, Hôpital Pitié-Salpêtrière, Assistance-Publique-Hôpitaux de Paris and Sorbonne University, Paris, France

    Marine Armand, Michaël Degaud & Frédéric Davi

  2. Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Inserm, Cell Death and Drug Resistance in Lymphoproliferative Disorders Team, F-75006, Paris, France

    Marine Armand, Michaël Degaud & Frédéric Davi

  3. Bioinformatics Department, LYSARC, Paris, France

    Bruno Tesson & Cécile Laurent

  4. Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutical Implications, INSERM UMR_S 1163, Imagine Institute, Université Paris Cité, Paris, France

    Manon Vavasseur, Olivier Hermine & Lucile Couronné

  5. Genomics Core Facility, Institut Imagine-Structure Fédérative de Recherche Necker, INSERM U1163 et INSERM US24/CNRS UAR3633, Paris Descartes Sorbonne Paris Cité University, Paris, France

    Mélanie Parisot

  6. Sorbonne-Université, INSERM, UMS-037 PASS, Cytometry Facility CyPS, Paris, France

    Bénédicte Hoareau-Coudert

  7. Department of Pathology, Hôpital Necker-Enfants Malades, Assistance-Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France

    Danielle Canioni

  8. Gustave Roussy Institute, Département des Innovations Thérapeutiques et Essais Précoces, Université Paris-Saclay, Villejuif, France

    Jean Marie Michot

  9. Unité mixte de recherche Inserm 1170, Université Paris-Saclay, Gustave Roussy Institute, Villejuif, France

    Jean Marie Michot

  10. Department of Pathology, Hôpital Pitié-Salpêtrière, Assistance-Publique-Hôpitaux de Paris, Sorbonne University, Paris, France

    Frédéric Charlotte

  11. Department of Pathology, Hôpital Saint-Louis, Assistance-Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France

    Véronique Meignin

  12. Department of Pathology, CHU de Toulouse, Institut Universitaire du Cancer, Toulouse, France

    Camille Laurent

  13. INSERM U1037, Centre de Recherche en Cancérologie de Toulouse, Toulouse, France

    Camille Laurent

  14. Université Lyon 1, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS, UMR5308, ENS Lyon, France

    Alexandra Traverse-Gléhen

  15. Hospices Civils de Lyon, Institut de Pathologie Multisite, Hôpital Lyon Sud, Lyon, France

    Alexandra Traverse-Gléhen

  16. Department of Pathology, Hôpitaux Universitaire Paris Centre, Cochin Hospital, Assistance Publique–Hôpitaux de Paris, Université Paris Cité, Paris, France

    Diane Damotte

  17. Department of Hematology, Hospices Civils de Lyon, Claude Bernard Lyon 1 University, Lyon, France

    Emmanuel Bachy

  18. INSERM U1111, Lymphoma-Immunobiology Biology (LIB) Team, International Center for Research in Infectious Diseases (CIRI), Lyon, France

    Emmanuel Bachy

  19. Department of Hematology and Oncology, Centre Hospitalier de Versailles, Le Chesnay, France

    Caroline Besson

  20. Université Paris-Saclay, UVSQ, Inserm, Équipe “Exposome et Hérédité”, CESP, Villejuif, France

    Caroline Besson

  21. Department of Hematology, Hôpital Necker–Enfants Malades, Assistance-Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France

    Olivier Hermine

  22. Laboratory of Onco-Hematology, Hôpital Necker–Enfants Malades, Assistance Publique–Hôpitaux de Paris, Université Paris Cité, Paris, France

    Lucile Couronné

Authors
  1. Marine Armand
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  2. Michaël Degaud
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Contributions

LC, OH and FD designed the study; MA, MD, FD and LC interpreted the data; MD performed DNA extraction from tumor samples; BT and CL performed the bioinformatics and biostatistics analyses; MV performed the Sanger sequencing; MP conducted the NGS experiments; BH-C was responsible of the cell-sorting experiments; J-MM and CB collected the clinical data; DC, FC, VM, CL, AT-G and DD provided tumor samples and performed histopathological reviews; CB, EB and OH participated in critical revision of the manuscript; MA, MD, FD and LC wrote the manuscript. All authors contributed to the article and approved the submitted version.

Corresponding author

Correspondence to Lucile Couronné.

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Armand, M., Degaud, M., Tesson, B. et al. Exploring the genetic landscape of HCV-related B-cell lymphomas using whole exome sequencing. Leukemia 37, 1388–1391 (2023). https://doi.org/10.1038/s41375-023-01868-2

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