| Lentiviral vector-based insertional mutagenesis identifies genes associated with liver cancer. | |
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MedLine Citation:
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PMID: 23314173 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2013-01-13 |
Journal Detail:
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Title: Nature methods Volume: 10 ISSN: 1548-7105 ISO Abbreviation: Nat. Methods Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-01-30 Completed Date: 2013-03-28 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 101215604 Medline TA: Nat Methods Country: United States |
Other Details:
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Languages: eng Pagination: 155-61 Citation Subset: IM |
Affiliation:
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San Raffaele-Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, Milan, Italy. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GEO/GSE31409 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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