Evolution under Spatially Heterogeneous Selection in Solid Tumors

	Evolution under Spatially Heterogeneous Selection in Solid Tumors
	Li, GH; Yang, ZY; Wu, DF; Liu, SX; Li, XN; Li, T; Li, YW; Liang, LJ; Zou, WL; Wu, C; Wang, HY; Lu, XM
	2022
发表期刊	MOLECULAR BIOLOGY AND EVOLUTION
ISSN	0737-4038
卷号	39 期号:1
摘要	Spatial genetic and phenotypic diversity within solid tumors has been well documented. Nevertheless, how this heterogeneity affects temporal dynamics of tumorigenesis has not been rigorously examined because solid tumors do not evolve as the standard population genetic model due to the spatial constraint. We therefore, propose a neutral spatial (NS) model whereby the mutation accumulation increases toward the periphery; the genealogical relationship is spatially determined and the selection efficacy is blunted (due to kin competition). In this model, neutral mutations are accrued and spatially distributed in manners different from those of advantageous mutations. Importantly, the distinctions could be blurred in the conventional model. To test the NS model, we performed a three-dimensional multiple microsampling of two hepatocellular carcinomas. Whole-genome sequencing (WGS) revealed a 2-fold increase in mutations going from the center to the periphery. The operation of natural selection can then be tested by examining the spatially determined clonal relationships and the clonal sizes. Due to limited migration, only the expansion of highly advantageous clones can sweep through a large part of the tumor to reveal the selective advantages. Hence, even multiregional sampling can only reveal a fraction of fitness differences in solid tumors. Our results suggest that the NS patterns are crucial for testing the influence of natural selection during tumorigenesis, especially for small solid 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/152453/13143
专题	科研部门_适应性进化与进化医学（吕雪梅）昆明动物研究所
推荐引用方式 GB/T 7714	Li, GH,Yang, ZY,Wu, DF,et al. Evolution under Spatially Heterogeneous Selection in Solid Tumors[J]. MOLECULAR BIOLOGY AND EVOLUTION,2022,39(1).
APA	Li, GH.,Yang, ZY.,Wu, DF.,Liu, SX.,Li, XN.,...&Lu, XM.(2022).Evolution under Spatially Heterogeneous Selection in Solid Tumors.MOLECULAR BIOLOGY AND EVOLUTION,39(1).
MLA	Li, GH,et al."Evolution under Spatially Heterogeneous Selection in Solid Tumors".MOLECULAR BIOLOGY AND EVOLUTION 39.1(2022).

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
2023022110.pdf（1687KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文