Use of signals of positive and negative selection to distinguish cancer genes and passenger genes

Abstract
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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.

The following previously published data sets were used

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Author details

László Bányai

Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary

Competing interests
The authors declare that no competing interests exist.
Maria Trexler

Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary

Competing interests
The authors declare that no competing interests exist.
Krisztina Kerekes

Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary

Competing interests
The authors declare that no competing interests exist.
Orsolya Csuka

Department of Pathogenetics, National Institute of Oncology, Budapest, Hungary

Competing interests
The authors declare that no competing interests exist.
László Patthy

Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary

For correspondence
patthy.laszlo@ttk.mta.hu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-1329-0484

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.

Copyright

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.