The theory of massively repeated evolution and full identifications of cancer-driving nucleotides (CDNs).

Autor:	Zhang L; State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China., Deng T; State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China., Liufu Z; State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.; State Key Laboratory of Genetic Resources and Evolution/Yunnan Key Laboratory of Biodiversity Information, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, China., Liu X; State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China., Chen B; State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.; GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China., Hu Z; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China., Liu C; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China., Tracy ME; State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China., Lu X; State Key Laboratory of Genetic Resources and Evolution/Yunnan Key Laboratory of Biodiversity Information, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, China., Wen HJ; State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.; Innovation Center for Evolutionary Synthetic Biology, Sun Yat-sen University, Guangzhou, China., Wu CI; State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.; Innovation Center for Evolutionary Synthetic Biology, Sun Yat-sen University, Guangzhou, China.; Department of Ecology and Evolution, University of Chicago, Chicago, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2024 Dec 17; Vol. 13. Date of Electronic Publication: 2024 Dec 17.
DOI:	10.7554/eLife.99340
Abstrakt:	Tumorigenesis, like most complex genetic traits, is driven by the joint actions of many mutations. At the nucleotide level, such mutations are cancer-driving nucleotides (CDNs). The full sets of CDNs are necessary, and perhaps even sufficient, for the understanding and treatment of each cancer patient. Currently, only a small fraction of CDNs is known as most mutations accrued in tumors are not drivers. We now develop the theory of CDNs on the basis that cancer evolution is massively repeated in millions of individuals. Hence, any advantageous mutation should recur frequently and, conversely, any mutation that does not is either a passenger or deleterious mutation. In the TCGA cancer database (sample size n =300-1000), point mutations may recur in i out of n patients. This study explores a wide range of mutation characteristics to determine the limit of recurrences ( i * ) driven solely by neutral evolution. Since no neutral mutation can reach i * =3, all mutations recurring at i ≥3 are CDNs. The theory shows the feasibility of identifying almost all CDNs if n increases to 100,000 for each cancer type. At present, only <10% of CDNs have been identified. When the full sets of CDNs are identified, the evolutionary mechanism of tumorigenesis in each case can be known and, importantly, gene targeted therapy will be far more effective in treatment and robust against drug resistance. Competing Interests: LZ, TD, ZL, XL, BC, ZH, CL, MT, XL, HW, CW No competing interests declared (© 2024, Zhang et al.)
Databáze:	MEDLINE
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