A Direct Test of Selection in Cell Populations Using the Diversity in Gene Expression within Tumors

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	A Direct Test of Selection in Cell Populations Using the Diversity in Gene Expression within Tumors
	Li, CY; Hou, YL; Xu, J; Zhang, AQ; Liu, ZZ; Qi, FR; Yang, ZY; Chen, K; Liu, SX; Huang, HW; Wang, QF; Dong, JH; Wu, CI; Lu, XM
	2017
发表期刊	MOLECULAR BIOLOGY AND EVOLUTION
ISSN	0737-4038
卷号	34 期号:7 页码:1730-1742
摘要	Although intratumor diversity driven by selection has been the prevailing view in cancer biology, recent population genetic analyses have been unable to reject the neutral interpretation. As the power to reject neutrality in tumors is often low, it will be desirable to have an alternative means to test selection directly. Here, we utilize gene expression data as a surrogate for functional significance in intra-and intertumor comparisons. The expression divergence between samples known to be driven by selection (e.g., between tumor and normal tissues) is always higher than the divergence between normal samples, which should be close to the neutral level of divergence. In contrast, the expression differentiation between regions of the same tumor, being lower than the neutral divergence, is incompatible with the hypothesis of selectively driven divergence. To further test the hypothesis of neutral evolution, we select a hepatocellular carcinoma tumor that has large intratumor SNV and CNV (single nucleotide variation and copy number variation, respectively) diversity. This tumor enables us to calibrate the level of expression divergence against that of genetic divergence. We observe that intratumor divergence in gene expression profile lags far behind genetic divergence, indicating insufficient phenotypic differences for selection to operate. All these expression analyses corroborate that natural selection does not operate effectively within tumors, supporting recent interpretations of within-tumor diversity. As the expected level of genetic diversity, hence the potential for drug resistance, would be much higher under neutrality than under selection, the issue is of both theoretical and clinical significance.
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/152453/13652
专题	个人在本单位外知识产出
推荐引用方式 GB/T 7714	Li, CY,Hou, YL,Xu, J,et al. A Direct Test of Selection in Cell Populations Using the Diversity in Gene Expression within Tumors[J]. MOLECULAR BIOLOGY AND EVOLUTION,2017,34(7):1730-1742.
APA	Li, CY.,Hou, YL.,Xu, J.,Zhang, AQ.,Liu, ZZ.,...&Lu, XM.(2017).A Direct Test of Selection in Cell Populations Using the Diversity in Gene Expression within Tumors.MOLECULAR BIOLOGY AND EVOLUTION,34(7),1730-1742.
MLA	Li, CY,et al."A Direct Test of Selection in Cell Populations Using the Diversity in Gene Expression within Tumors".MOLECULAR BIOLOGY AND EVOLUTION 34.7(2017):1730-1742.

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2023041203.pdf（565KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文