Extremely high genetic diversity in a single tumor points to prevalence of non-Darwinian cell evolution

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	Extremely high genetic diversity in a single tumor points to prevalence of non-Darwinian cell evolution
	Ling, SP; Hu, Z; Yang, ZY; Yang, F; Li, YW; Lin, P; Chen, K; Dong, LL; Cao, LH; Tao, Y; Hao, LT; Chen, QJ; Gong, Q; Wu, DF; Li, WJ; Zhao, WM; Tian, XY; Hao, CY; Hungate, EA; Catenacci, DVT; Hudson, RR; Li, WH; Lu, XM; Wu, CI
	2015
发表期刊	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN	0027-8424
卷号	112 期号:47 页码:E6496-E6505
摘要	The prevailing view that the evolution of cells in a tumor is driven by Darwinian selection has never been rigorously tested. Because selection greatly affects the level of intratumor genetic diversity, it is important to assess whether intratumor evolution follows the Darwinian or the non-Darwinian mode of evolution. To provide the statistical power, many regions in a single tumor need to be sampled and analyzed much more extensively than has been attempted in previous intratumor studies. Here, from a hepatocellular carcinoma (HCC) tumor, we evaluated multiregional samples from the tumor, using either whole-exome sequencing (WES) (n = 23 samples) or genotyping (n = 286) under both the infinite-site and infinite-allele models of population genetics. In addition to the many single-nucleotide variations (SNVs) present in all samples, there were 35 polymorphic SNVs among samples. High genetic diversity was evident as the 23 WES samples defined 20 unique cell clones. With all 286 samples genotyped, clonal diversity agreed well with the non-Darwinian model with no evidence of positive Darwinian selection. Under the non-Darwinian model, MALL (the number of coding region mutations in the entire tumor) was estimated to be greater than 100 million in this tumor. DNA sequences reveal local diversities in small patches of cells and validate the estimation. In contrast, the genetic diversity under a Darwinian model would generally be orders of magnitude smaller. Because the level of genetic diversity will have implications on therapeutic resistance, non-Darwinian evolution should be heeded in cancer treatments even for microscopic tumors.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13655
专题	个人在本单位外知识产出
推荐引用方式 GB/T 7714	Ling, SP,Hu, Z,Yang, ZY,et al. Extremely high genetic diversity in a single tumor points to prevalence of non-Darwinian cell evolution[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2015,112(47):E6496-E6505.
APA	Ling, SP.,Hu, Z.,Yang, ZY.,Yang, F.,Li, YW.,...&Wu, CI.(2015).Extremely high genetic diversity in a single tumor points to prevalence of non-Darwinian cell evolution.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,112(47),E6496-E6505.
MLA	Ling, SP,et al."Extremely high genetic diversity in a single tumor points to prevalence of non-Darwinian cell evolution".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 112.47(2015):E6496-E6505.

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2023041206.pdf（1670KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文