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

  1. László Bányai
  2. Maria Trexler
  3. Krisztina Kerekes
  4. Orsolya Csuka
  5. László Patthy  Is a corresponding author
  1. Research Centre for Natural Sciences, Hungary
  2. 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.

The following previously published data sets were used

Article and author information

Author details

  1. László Bányai

    Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  2. Maria Trexler

    Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  3. Krisztina Kerekes

    Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  4. Orsolya Csuka

    Department of Pathogenetics, National Institute of Oncology, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  5. 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.
    ORCID icon "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.

Reviewing Editor

  1. Eduardo Eyras, Australian National University, Australia

Version history

  1. Received: June 3, 2020
  2. Accepted: January 10, 2021
  3. Accepted Manuscript published: January 11, 2021 (version 1)
  4. 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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  1. László Bányai
  2. Maria Trexler
  3. Krisztina Kerekes
  4. Orsolya Csuka
  5. László Patthy
(2021)
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

Share this article

https://doi.org/10.7554/eLife.59629

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