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Extensive heterogeneity in somatic mutation and selection in the human bladder.

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Title: Extensive heterogeneity in somatic mutation and selection in the human bladder.
Authors: Lawson, Andrew R. J., Abascal, Federico, Coorens, Tim H. H., Hooks, Yvette, O’Neill, Laura, Latimer, Calli, Raine, Keiran, Sanders, Mathijs A., Warren, Anne Y., Mahbubani, Krishnaa T. A., Bareham, Bethany, Butler, Timothy M., Harvey, Luke M. R., Cagan, Alex, Menzies, Andrew, Moore, Luiza, Colquhoun, Alexandra J., Turner, William, Thomas, Benjamin, Gnanapragasam, Vincent
Source: Science (pre-March 2025). 10/2/2020, Vol. 370 Issue 6512, p75-82. 8p. 4 Graphs.
Subjects: Somatic mutation, Clonal selection theory, Macrophages, Chromatin, Mutagens
Abstract: 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. [ABSTRACT FROM AUTHOR]
Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Extensive heterogeneity in somatic mutation and selection in the human bladder.
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  Data: <searchLink fieldCode="AR" term="%22Lawson%2C+Andrew+R%2E+J%2E%22">Lawson, Andrew R. J.</searchLink><br /><searchLink fieldCode="AR" term="%22Abascal%2C+Federico%22">Abascal, Federico</searchLink><br /><searchLink fieldCode="AR" term="%22Coorens%2C+Tim+H%2E+H%2E%22">Coorens, Tim H. H.</searchLink><br /><searchLink fieldCode="AR" term="%22Hooks%2C+Yvette%22">Hooks, Yvette</searchLink><br /><searchLink fieldCode="AR" term="%22O’Neill%2C+Laura%22">O’Neill, Laura</searchLink><br /><searchLink fieldCode="AR" term="%22Latimer%2C+Calli%22">Latimer, Calli</searchLink><br /><searchLink fieldCode="AR" term="%22Raine%2C+Keiran%22">Raine, Keiran</searchLink><br /><searchLink fieldCode="AR" term="%22Sanders%2C+Mathijs+A%2E%22">Sanders, Mathijs A.</searchLink><br /><searchLink fieldCode="AR" term="%22Warren%2C+Anne+Y%2E%22">Warren, Anne Y.</searchLink><br /><searchLink fieldCode="AR" term="%22Mahbubani%2C+Krishnaa+T%2E+A%2E%22">Mahbubani, Krishnaa T. A.</searchLink><br /><searchLink fieldCode="AR" term="%22Bareham%2C+Bethany%22">Bareham, Bethany</searchLink><br /><searchLink fieldCode="AR" term="%22Butler%2C+Timothy+M%2E%22">Butler, Timothy M.</searchLink><br /><searchLink fieldCode="AR" term="%22Harvey%2C+Luke+M%2E+R%2E%22">Harvey, Luke M. R.</searchLink><br /><searchLink fieldCode="AR" term="%22Cagan%2C+Alex%22">Cagan, Alex</searchLink><br /><searchLink fieldCode="AR" term="%22Menzies%2C+Andrew%22">Menzies, Andrew</searchLink><br /><searchLink fieldCode="AR" term="%22Moore%2C+Luiza%22">Moore, Luiza</searchLink><br /><searchLink fieldCode="AR" term="%22Colquhoun%2C+Alexandra+J%2E%22">Colquhoun, Alexandra J.</searchLink><br /><searchLink fieldCode="AR" term="%22Turner%2C+William%22">Turner, William</searchLink><br /><searchLink fieldCode="AR" term="%22Thomas%2C+Benjamin%22">Thomas, Benjamin</searchLink><br /><searchLink fieldCode="AR" term="%22Gnanapragasam%2C+Vincent%22">Gnanapragasam, Vincent</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 10/2/2020, Vol. 370 Issue 6512, p75-82. 8p. 4 Graphs.
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  Data: 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. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=146240779
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