Center of Excellence In Genomic Medicine Research | Researches | Identification of novel driver tumor suppressors through functional interrogation of putative passenger mutations in colorectal cancer

Center of Excellence In Genomic Medicine Research

Document Details

Document Type	:	Article In Journal
Document Title	:	Identification of novel driver tumor suppressors through functional interrogation of putative passenger mutations in colorectal cancer Identification of novel driver tumor suppressors through functional interrogation of putative passenger mutations in colorectal cancer
Document Language	:	English
Abstract	:	Cancer genome sequencing efforts are leading to the identification of genetic mutations in many types of malignancy. However, the majority of these genetic alterations have been considered random passengers that do not directly contribute to tumorigenesis. We have previously conducted a soft agar-based short hairpin RNA (shRNA) screen within colorectal cancer (CRC) candidate driver genes (CAN-genes) using a karyotypically diploid hTERT- and CDK4-immortalized human colonic epithelial cell (HCEC) model and discovered that depletion of 65 of the 151 CAN-genes enhanced anchorage-independent growth in HCECs with ectopic expression of K-Ras(V12) and/or TP53 knockdown. We now constructed an interaction map of the confirmed CAN-genes with CRC non-CAN-genes and screened for functional tumor suppressors. Remarkably, depletion of 15 out of 25 presumed passenger genes that interact with confirmed CAN-genes (60%) promoted soft agar growth in HCECs with TP53 knockdown compared to only 7 out of 55 (12.5%) of presumed passenger genes that do not interact. We have thus demonstrated a pool of driver mutations among the putative CRC passenger/incidental mutations, establishing the importance of employing biological filters, in addition to bioinformatics, to identify driver mutations
ISSN	:	1097-0215
Journal Name	:	International Journal of Cancer
Volume	:	132
Issue Number	:	3
Publishing Year	:	1434 AH 2013 AD
Article Type	:	Article
Added Date	:	Tuesday, March 8, 2016

Researchers

Researcher Name (Arabic)	Researcher Name (English)	Researcher Type	Dr Grade	Email
Lu Zhang	Zhang, Lu	Investigator
Kakajan Komurov	Komurov, Kakajan	Researcher
Woodring E Wright	Wright, Woodring E	Researcher
Jerry W Shay	Shay, Jerry W	Researcher

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File Name	Type	Description
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