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Updated: May 15, 2026

Identification of Functionally-Relevant Lentivirus Integration Sites in an Insertional Mutagenesis Cell Library
Published on: January 10, 2025
Lentiviral vector-based insertional mutagenesis identifies genes associated with liver cancer
Marco Ranzani1, Daniela Cesana, Cynthia C Bartholomae
1San Raffaele-Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.
None:
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.
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