Burghel, G.J., Lin, W-Y., Whitehouse, H. et al. (6 more authors) (2013) Identification of Candidate Driver Genes in Common Focal Chromosomal Aberrations of Microsatellite Stable Colorectal Cancer. PLOS ONE, 8 (12). UNSP e83859. ISSN 1932-6203
Abstract
Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide. Chromosomal instability (CIN) is a major driving force of microsatellite stable (MSS) sporadic CRC. CIN tumours are characterised by a large number of somatic chromosomal copy number aberrations (SCNA) that frequently affect oncogenes and tumour suppressor genes. The main aim of this work was to identify novel candidate CRC driver genes affected by recurrent and focal SCNA. High resolution genome-wide comparative genome hybridisation (CGH) arrays were used to compare tumour and normal DNA for 53 sporadic CRC cases. Context corrected common aberration (COCA) analysis and custom algorithms identified 64 deletions and 32 gains of focal minimal common regions (FMCR) at high frequency (>10%). Comparison of these FMCR with published genomic profiles from CRC revealed common overlap (42.2% of deletions and 34.4% of copy gains). Pathway analysis showed that apoptosis and p53 signalling pathways were commonly affected by deleted FMCR, and MAPK and potassium channel pathways by gains of FMCR. Candidate tumour suppressor genes in deleted FMCR included RASSF3, IFNAR1, IFNAR2 and NFKBIA and candidate oncogenes in gained FMCR included PRDM16, TNS1, RPA3 and KCNMA1. In conclusion, this study confirms some previously identified aberrations in MSS CRC and provides in silico evidence for some novel candidate driver genes
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication (https://creativecommons.org/publicdomain/zero/1.0/). |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 03 Aug 2016 15:28 |
Last Modified: | 03 Aug 2016 15:28 |
Published Version: | http://dx.doi.org/10.1371/journal.pone.0083859 |
Status: | Published |
Publisher: | Public Library of Science |
Refereed: | Yes |
Identification Number: | 10.1371/journal.pone.0083859 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:95625 |
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Licence: Creative Commons: Public Domain Dedication