Macroscopic somatic clonal expansion in morphologically normal human urothelium

doi:10.1126/science.aba7300

GSTDTAP > 气候变化

DOI	10.1126/science.aba7300
	Macroscopic somatic clonal expansion in morphologically normal human urothelium
	Ruoyan Li; Yiqing Du; Zhanghua Chen; Deshu Xu; Tianxin Lin; Shanzhao Jin; Gongwei Wang; Ziyang Liu; Min Lu; Xu Chen; Tao Xu; Fan Bai
	2020-10-02
发表期刊	Science
出版年	2020
英文摘要	Depending on the environment of the individual, the human bladder can be exposed to carcinogens as they are flushed through the body. Lawson et al. and Li et al. examined the genetic composition of laser-dissected microbiopsies from normal and cancer cells collected from the urothelium, a specialized epithelium lining the lower urinary tract (see the Perspective by Rozen). These complementary studies identified the mutational landscape of bladder urothelium through various sequencing strategies and identified high mutational heterogeneity within and between individuals and tumors. Both studies identified mutational profiles related to specific carcinogens such as aristolochic acid and the molecules found in tobacco. These studies present a comprehensive description of the diverse mutational landscape of the human bladder in health and disease, unraveling positive selection for cancer-causing mutations, a diversity of mutational processes, and large differences across individuals. Science , this issue p. [75][1], p. [82][2]; see also p. [34][3] Knowledge of somatic mutation accumulation in normal cells, which is essential for understanding cancer development and evolution, remains largely lacking. In this study, we investigated somatic clonal events in morphologically normal human urothelium (MNU; epithelium lining the bladder and ureter) and identified macroscopic clonal expansions. Aristolochic acid (AA), a natural herb-derived compound, was a major mutagenic driving factor in MNU. AA drastically accelerates mutation accumulation and enhances clonal expansion. Mutations in MNU were widely observed in chromatin remodeling genes such as KMT2D and KDM6A but rarely in TP53 , PIK3CA , and FGFR3 . KMT2D mutations were found to be common in urothelial cells, regardless of whether the cells experience exogenous mutagen exposure. Copy number alterations were rare and largely confined to small-scale regions, along with copy-neutral loss of heterozygosity. Single AA-associated clones in MNU expanded to a scale of several square centimeters in size. [1]: /lookup/doi/10.1126/science.aba8347 [2]: /lookup/doi/10.1126/science.aba7300 [3]: /lookup/doi/10.1126/science.abe0955
领域	气候变化 ; 资源环境
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文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/298056
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Ruoyan Li,Yiqing Du,Zhanghua Chen,et al. Macroscopic somatic clonal expansion in morphologically normal human urothelium[J]. Science,2020.
APA	Ruoyan Li.,Yiqing Du.,Zhanghua Chen.,Deshu Xu.,Tianxin Lin.,...&Fan Bai.(2020).Macroscopic somatic clonal expansion in morphologically normal human urothelium.Science.
MLA	Ruoyan Li,et al."Macroscopic somatic clonal expansion in morphologically normal human urothelium".Science (2020).