Use of signals of positive and negative selection to distinguish cancer genes and passenger genes
- Research Centre for Natural Sciences, Hungary
- National Institute of Oncology, Hungary
Abstract
A major goal of cancer genomics is to identify all genes that play critical roles in carcinogenesis. Most approaches focused on genes positively selected for mutations that drive carcinogenesis and neglected the role of negative selection. Some studies have actually concluded that negative selection has no role in cancer evolution. We have re-examined the role of negative selection in tumor evolution through the analysis of the patterns of somatic mutations affecting the coding sequences of human genes. Our analyses have confirmed that tumor suppressor genes are positively selected for inactivating mutations, oncogenes, however, were found to display signals of both negative selection for inactivating mutations and positive selection for activating mutations. Significantly, we have identified numerous human genes that show signs of strong negative selection during tumor evolution, suggesting that their functional integrity is essential for the growth and survival of tumor cells.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
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COSMIC: the Catalogue Of Somatic Mutations In CancerCOSMIC the Catalogue Of Somatic Mutations In Cancer.
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dbSNP: the NCBI database of genetic variationdbSNP: the NCBI database of genetic variation.
Article and author information
Author details
Funding
Hungarian National Research, Development and Innovation Office (GINOP-2.3.2-15-2016-00001)
- László Bányai
- Maria Trexler
- Krisztina Kerekes
- László Patthy
Hungarian National Research, Development and Innovation Office (NVKP_16-1-2016-0005)
- Orsolya Csuka
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Eduardo Eyras, Australian National University, Australia
Version history
- Received: June 3, 2020
- Accepted: January 10, 2021
- Accepted Manuscript published: January 11, 2021 (version 1)
- Version of Record published: February 11, 2021 (version 2)
Copyright
© 2021, Bányai et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Use of signals of positive and negative selection to distinguish cancer genes and passenger genes
eLife 10:e59629.
https://doi.org/10.7554/eLife.59629
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