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Quantification of subclonal selection in cancer from bulk sequencing data

Williams, MJ; Werner, B; Heide, T; Curtis, C; Barnes, CP; Sottoriva, A; Graham, TA; (2018) Quantification of subclonal selection in cancer from bulk sequencing data. Nature Genetics , 50 (6) pp. 895-903. 10.1038/s41588-018-0128-6. Green open access

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Abstract

Subclonal architectures are prevalent across cancer types. However, the temporal evolutionary dynamics that produce tumor subclones remain unknown. Here we measure clone dynamics in human cancers by using computational modeling of subclonal selection and theoretical population genetics applied to high-throughput sequencing data. Our method determined the detectable subclonal architecture of tumor samples and simultaneously measured the selective advantage and time of appearance of each subclone. We demonstrate the accuracy of our approach and the extent to which evolutionary dynamics are recorded in the genome. Application of our method to high-depth sequencing data from breast, gastric, blood, colon and lung cancer samples, as well as metastatic deposits, showed that detectable subclones under selection, when present, consistently emerged early during tumor growth and had a large fitness advantage (>20%). Our quantitative framework provides new insight into the evolutionary trajectories of human cancers and facilitates predictive measurements in individual tumors from widely available sequencing data.

Type: Article
Title: Quantification of subclonal selection in cancer from bulk sequencing data
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41588-018-0128-6
Publisher version: http://doi.org/10.1038/s41588-018-0128-6
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10050192
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