Gilroy, K. L. et al. (2016) Gamma-retrovirus integration marks cell type-specific cancer genes: a novel profiling tool in cancer genomics. PLoS ONE, 11(4), e0154070. (doi: 10.1371/journal.pone.0154070) (PMID:27097319) (PMCID:PMC4838236)
|
Text
118628.pdf - Published Version Available under License Creative Commons Attribution. 2MB |
Abstract
Retroviruses have been foundational in cancer research since early studies identified proto-oncogenes as targets for insertional mutagenesis. Integration of murine gamma-retroviruses into the host genome favours promoters and enhancers and entails interaction of viral integrase with host BET/bromodomain factors. We report that this integration pattern is conserved in feline leukaemia virus (FeLV), a gamma-retrovirus that infects many human cell types. Analysis of FeLV insertion sites in the MCF-7 mammary carcinoma cell line revealed strong bias towards active chromatin marks with no evidence of significant post-integration growth selection. The most prominent FeLV integration targets had little overlap with the most abundantly expressed transcripts, but were strongly enriched for annotated cancer genes. A meta-analysis based on several gamma-retrovirus integration profiling (GRIP) studies in human cells (CD34+, K562, HepG2) revealed a similar cancer gene bias but also remarkable cell-type specificity, with prominent exceptions including a universal integration hotspot at the long non-coding RNA MALAT1. Comparison of GRIP targets with databases of super-enhancers from the same cell lines showed that these have only limited overlap and that GRIP provides unique insights into the upstream drivers of cell growth. These observations elucidate the oncogenic potency of the gamma-retroviruses and support the wider application of GRIP to identify the genes and growth regulatory circuits that drive distinct cancer types.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Cameron, Professor Ewan and Neil, Professor James and Naseer, Dr Asif and Kilbey, Dr Anna and Gilroy, Dr Kathryn and Terry, Mrs Anne |
| Authors: | Gilroy, K. L., Terry, A., Naseer, A., de Ridder, J., Allahyar, A., Wang, W., Carpenter, E., Mason, A., Wong, G. K.-S., Cameron, E. R., Kilbey, A., and Neil, J. C. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | PLoS ONE |
| Publisher: | Public Library of Science |
| ISSN: | 1932-6203 |
| ISSN (Online): | 1932-6203 |
| Published Online: | 20 April 2016 |
| Copyright Holders: | Copyright © 2016 The Authors |
| First Published: | First published in PLoS ONE 11(4): e0154070 |
| Publisher Policy: | Reproduced under a Creative Commons License |
University Staff: Request a correction | Enlighten Editors: Update this record
Funder and Project Information
Funder and Project Information