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Cancers 2016, 8(11), 99; doi:10.3390/cancers8110099

Identifying Cancer Driver Genes Using Replication-Incompetent Retroviral Vectors

1
College of Pharmacy, Washington State University, WSU Spokane PBS 323, P.O. Box 1495, Spokane, WA 99210, USA
2
School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Samuel C. Mok
Received: 20 August 2016 / Revised: 12 October 2016 / Accepted: 17 October 2016 / Published: 25 October 2016
View Full-Text   |   Download PDF [1570 KB, uploaded 25 October 2016]   |  

Abstract

Identifying novel genes that drive tumor metastasis and drug resistance has significant potential to improve patient outcomes. High-throughput sequencing approaches have identified cancer genes, but distinguishing driver genes from passengers remains challenging. Insertional mutagenesis screens using replication-incompetent retroviral vectors have emerged as a powerful tool to identify cancer genes. Unlike replicating retroviruses and transposons, replication-incompetent retroviral vectors lack additional mutagenesis events that can complicate the identification of driver mutations from passenger mutations. They can also be used for almost any human cancer due to the broad tropism of the vectors. Replication-incompetent retroviral vectors have the ability to dysregulate nearby cancer genes via several mechanisms including enhancer-mediated activation of gene promoters. The integrated provirus acts as a unique molecular tag for nearby candidate driver genes which can be rapidly identified using well established methods that utilize next generation sequencing and bioinformatics programs. Recently, retroviral vector screens have been used to efficiently identify candidate driver genes in prostate, breast, liver and pancreatic cancers. Validated driver genes can be potential therapeutic targets and biomarkers. In this review, we describe the emergence of retroviral insertional mutagenesis screens using replication-incompetent retroviral vectors as a novel tool to identify cancer driver genes in different cancer types. View Full-Text
Keywords: insertional mutagenesis; replication-incompetent retroviral vector; gammaretroviral (γRV) vector; lentiviral (LV) vector; cancer driver genes; drug targets; biomarker insertional mutagenesis; replication-incompetent retroviral vector; gammaretroviral (γRV) vector; lentiviral (LV) vector; cancer driver genes; drug targets; biomarker
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Bii, V.M.; Trobridge, G.D. Identifying Cancer Driver Genes Using Replication-Incompetent Retroviral Vectors. Cancers 2016, 8, 99.

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