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.
- László Bányai
- Maria Trexler
- Krisztina Kerekes
- László Patthy
- Orsolya Csuka
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Eduardo Eyras, Australian National University, Australia
- Received: June 3, 2020
- Accepted: January 10, 2021
- Accepted Manuscript published: January 11, 2021 (version 1)
© 2021, Bányai et al.
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