A major goal of cancer genomics is to identify all genes that play critical roles in carcinogenesis. Most approaches focused on genes that are 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. In the present work 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.

中文翻译：

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利用正负选择信号区分癌症基因和过客基因

癌症基因组学的主要目标是鉴定在癌变过程中起关键作用的所有基因。大多数方法集中于为驱动致癌作用的突变阳性选择的基因，而忽略了阴性选择的作用。实际上，一些研究得出的结论是，阴性选择在癌症进化中没有作用。在本工作中，我们通过分析影响人类基因编码序列的体细胞突变模式，重新审查了阴性选择在肿瘤进化中的作用。我们的分析已经证实，为抑制突变，积极选择了抑癌基因。然而，发现致癌基因显示出用于失活突变的负选择和用于激活突变的正选择信号。重要的是