TY - JOUR TI - Use of signals of positive and negative selection to distinguish cancer genes and passenger genes AU - Bányai, László AU - Trexler, Maria AU - Kerekes, Krisztina AU - Csuka, Orsolya AU - Patthy, László A2 - Eyras, Eduardo A2 - Wittkopp, Patricia J VL - 10 PY - 2021 DA - 2021/01/11 SP - e59629 C1 - eLife 2021;10:e59629 DO - 10.7554/eLife.59629 UR - https://doi.org/10.7554/eLife.59629 AB - 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. KW - cancer gene KW - negative selection KW - positive selection KW - passenger gene KW - neutral evolution JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -