Lentiviral vector-based insertional mutagenesis identifies genes associated with liver cancer

Marco Ranzani, Daniela Cesana, Cynthia C. Bartholomae, Francesca Sanvito, Mauro Pala, Fabrizio Benedicenti, Pierangela Gallina, Lucia Sergi Sergi, Stefania Merella, Alessandro Bulfone, Claudio Doglioni, Christof Von Kalle, Yoon Jun Kim, Manfred Schmidt, Giovanni Tonon, Luigi Naldini, Eugenio Montini

Research output: Contribution to journalArticle

Abstract

Transposons and γ-retroviruses have been efficiently used as insertional mutagens in different tissues to identify molecular culprits of cancer. However, these systems are characterized by recurring integrations that accumulate in tumor cells and that hamper the identification of early cancer-driving events among bystander and progression-related events. We developed an insertional mutagenesis platform based on lentiviral vectors (LVVs) by which we could efficiently induce hepatocellular carcinoma (HCC) in three different mouse models. By virtue of the LVV's replication-deficient nature and broad genome-wide integration pattern, LVV-based insertional mutagenesis allowed identification of four previously unknown liver cancer-associated genes from a limited number of integrations. We validated the oncogenic potential of all the identified genes in vivo, with different levels of penetrance. The newly identified genes are likely to play a role in human cancer because they are upregulated, amplified and/or deleted in human HCCs and can predict clinical outcomes of patients.

Original languageEnglish
Pages (from-to)155-161
Number of pages7
JournalNature Methods
Volume10
Issue number2
DOIs
Publication statusPublished - Feb 2013

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology
  • Biochemistry
  • Cell Biology

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  • Cite this

    Ranzani, M., Cesana, D., Bartholomae, C. C., Sanvito, F., Pala, M., Benedicenti, F., Gallina, P., Sergi, L. S., Merella, S., Bulfone, A., Doglioni, C., Von Kalle, C., Kim, Y. J., Schmidt, M., Tonon, G., Naldini, L., & Montini, E. (2013). Lentiviral vector-based insertional mutagenesis identifies genes associated with liver cancer. Nature Methods, 10(2), 155-161. https://doi.org/10.1038/nmeth.2331