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DeCiFering the elusive cancer cell fraction in tumor heterogeneity and evolution

Satas, G; Zaccaria, S; El-Kebir, M; Raphael, BJ; (2021) DeCiFering the elusive cancer cell fraction in tumor heterogeneity and evolution. Cell Systems , 12 (10) 1004-1018.e10. 10.1016/j.cels.2021.07.006. Green open access

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Abstract

The cancer cell fraction (CCF), or proportion of cancerous cells in a tumor containing a single-nucleotide variant (SNV), is a fundamental statistic used to quantify tumor heterogeneity and evolution. Existing CCF estimation methods from bulk DNA sequencing data assume that every cell with an SNV contains the same number of copies of the SNV. This assumption is unrealistic in tumors with copy-number aberrations that alter SNV multiplicities. Furthermore, the CCF does not account for SNV losses due to copy-number aberrations, confounding downstream phylogenetic analyses. We introduce DeCiFer, an algorithm that overcomes these limitations by clustering SNVs using a novel statistic, the descendant cell fraction (DCF). The DCF quantifies both the prevalence of an SNV at the present time and its past evolutionary history using an evolutionary model that allows mutation losses. We show that DeCiFer yields more parsimonious reconstructions of tumor evolution than previously reported for 49 prostate cancer samples.

Type: Article
Title: DeCiFering the elusive cancer cell fraction in tumor heterogeneity and evolution
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cels.2021.07.006
Publisher version: https://doi.org/10.1016/j.cels.2021.07.006
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.
Keywords: cancer genomics, clustering, cancer cell fraction, algorithm, single-nucleotide variants, copy-number aberrations, tumor heterogeneity
UCL classification: UCL
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 Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
URI: https://discovery.ucl.ac.uk/id/eprint/10138101
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