Document Detail


Lentiviral vector-based insertional mutagenesis identifies genes associated with liver cancer.
MedLine Citation:
PMID:  23314173     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-13
Journal Detail:
Title:  Nature methods     Volume:  10     ISSN:  1548-7105     ISO Abbreviation:  Nat. Methods     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-30     Completed Date:  2013-03-28     Revised Date:  2013-04-16    
Medline Journal Info:
Nlm Unique ID:  101215604     Medline TA:  Nat Methods     Country:  United States    
Other Details:
Languages:  eng     Pagination:  155-61     Citation Subset:  IM    
Affiliation:
San Raffaele-Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.
Data Bank Information
Bank Name/Acc. No.:
GEO/GSE31409
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MeSH Terms
Descriptor/Qualifier:
Animals
Carcinoma, Hepatocellular / genetics*
Cyclin-Dependent Kinase Inhibitor p16 / deficiency
Genetic Vectors
Humans
Lentivirus / genetics*
Liver Neoplasms / genetics*
Mice
Mutagenesis, Insertional*
Oncogenes*
PTEN Phosphohydrolase / deficiency
Prealbumin / genetics
Receptor, Interferon alpha-beta / deficiency
Chemical
Reg. No./Substance:
0/Cdkn2a protein, mouse; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/Ifnar1 protein, mouse; 0/Prealbumin; 156986-95-7/Receptor, Interferon alpha-beta; EC 3.1.3.48/Pten protein, mouse; EC 3.1.3.67/PTEN Phosphohydrolase

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