Extensive heterogeneity in somatic mutation and selection in the human bladder

doi:10.1126/science.aba8347

GSTDTAP > 气候变化

DOI	10.1126/science.aba8347
	Extensive heterogeneity in somatic mutation and selection in the human bladder
	Andrew R. J. Lawson; Federico Abascal; Tim H. H. Coorens; Yvette Hooks; Laura O’Neill; Calli Latimer; Keiran Raine; Mathijs A. Sanders; Anne Y. Warren; Krishnaa T. A. Mahbubani; Bethany Bareham; Timothy M. Butler; Luke M. R. Harvey; Alex Cagan; Andrew Menzies; Luiza Moore; Alexandra J. Colquhoun; William Turner; Benjamin Thomas; Vincent Gnanapragasam; Nicholas Williams; Doris M. Rassl; Harald Vöhringer; Sonia Zumalave; Jyoti Nangalia; José M. C. Tubío; Moritz Gerstung; Kourosh Saeb-Parsy; Michael R. Stratton; Peter J. Campbell; Thomas J. Mitchell; Iñigo Martincorena
	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] The extent of somatic mutation and clonal selection in the human bladder remains unknown. We sequenced 2097 bladder microbiopsies from 20 individuals using targeted ( n = 1914 microbiopsies), whole-exome ( n = 655), and whole-genome ( n = 88) sequencing. We found widespread positive selection in 17 genes. Chromatin remodeling genes were frequently mutated, whereas mutations were absent in several major bladder cancer genes. There was extensive interindividual variation in selection, with different driver genes dominating the clonal landscape across individuals. Mutational signatures were heterogeneous across clones and individuals, which suggests differential exposure to mutagens in the urine. Evidence of APOBEC mutagenesis was found in 22% of the microbiopsies. Sequencing multiple microbiopsies from five patients with bladder cancer enabled comparisons with cancer-free individuals and across histological features. This study reveals a rich landscape of mutational processes and selection in normal urothelium with large heterogeneity across clones and individuals. [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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引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/298055
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Andrew R. J. Lawson,Federico Abascal,Tim H. H. Coorens,et al. Extensive heterogeneity in somatic mutation and selection in the human bladder[J]. Science,2020.
APA	Andrew R. J. Lawson.,Federico Abascal.,Tim H. H. Coorens.,Yvette Hooks.,Laura O’Neill.,...&Iñigo Martincorena.(2020).Extensive heterogeneity in somatic mutation and selection in the human bladder.Science.
MLA	Andrew R. J. Lawson,et al."Extensive heterogeneity in somatic mutation and selection in the human bladder".Science (2020).