Evolutionary Origins of Cancer Driver Genes and Implications for Cancer Prognosis

Abstract

The cancer atavistic theory suggests that carcinogenesis is a reverse evolution process. It is thus of great interest to explore the evolutionary origins of cancer driver genes and the relevant mechanisms underlying the carcinogenesis. Moreover, the evolutionary features of cancer driver genes could be helpful in selecting cancer biomarkers from high-throughput data. In this study, through analyzing the cancer endogenous molecular networks, we revealed that the subnetwork originating from eukaryota could control the unlimited proliferation of cancer cells, and the subnetwork originating from eumetazoa could recapitulate the other hallmarks of cancer. In addition, investigations based on multiple datasets revealed that cancer driver genes were enriched in genes originating from eukaryota, opisthokonta, and eumetazoa. These results have important implications for enhancing the robustness of cancer prognosis models through selecting the gene signatures by the gene age information.

Ancient evolutionary origin of intrinsically disordered cancer risk regions

“…Estimation of evolutionary origin can also be complicated by gene loss and depend on the availability of genome sequences. The evolutionary origin of CBL was predicted previously to be the emergence time of opisthokonts [58] , however our results show an eumetazoa origin. On the one hand, the CBL protein family indeed has ancient origin with a predicted ortholog from Dictyostelium, which in fact means a more ancient, Eukaryota origin.…”

The Network of Cancer Genes (NCG): a comprehensive catalogue of known and candidate cancer genes from cancer sequencing screens

“…Cancer genes, and in particular candidate cancer genes, originated earlier in evolution (Fig. 4b) [37, 58, 59]. Known cancer genes alone do not differ from the rest due to the fact that OGs are significantly younger than TSGs (Fig.…”

Blood Cell DNA Methylation of Aging-Related Ubiquitination Gene DZIP3 Can Predict the Onset of Early Stage Colorectal Cancer

“…The results showed that the ubiquitination regulatory gene DZIP3 was significantly correlated with age and changes in immune cell components. In addition, previous studies have shown that genes originating in different stages have different biological functions, which are closely related to human phenotypes (40)(41)(42)(43)(44)(45). Therefore, the evolutionary information of genes often implies important clues to the analysis of human disease mechanisms (40,41,44).…”

“…In addition, previous studies have shown that genes originating in different stages have different biological functions, which are closely related to human phenotypes (40)(41)(42)(43)(44)(45). Therefore, the evolutionary information of genes often implies important clues to the analysis of human disease mechanisms (40,41,44). For example, a study had shown that the gene network composed of eumetazoa-originated genes can regulate the hallmarks of cancer (44), reflecting the potential associations of eumetazoaoriginated genes with cancer.…”