High-definition reconstruction of clonal composition in cancer

Fischer, A., Vázquez-García, I., Illingworth, C. J.R. and Mustonen, V. (2014) High-definition reconstruction of clonal composition in cancer. Cell Reports, 7(5), pp. 1740-1752. (doi: 10.1016/j.celrep.2014.04.055) (PMID:24882004) (PMCID:PMC4062932)

Abstract

The extensive genetic heterogeneity of cancers can greatly affect therapy success due to the existence of subclonal mutations conferring resistance. However, the characterization of subclones in mixed-cell populations is computationally challenging due to the short length of sequence reads that are generated by current sequencing technologies. Here, we report cloneHD, a probabilistic algorithm for the performance of subclone reconstruction from data generated by high-throughput DNA sequencing: read depth, B-allele counts at germline heterozygous loci, and somatic mutation counts. The algorithm can exploit the added information present in correlated longitudinal or multiregion samples and takes into account correlations along genomes caused by events such as copy-number changes. We apply cloneHD to two case studies: a breast cancer sample and time-resolved samples of chronic lymphocytic leukemia, where we demonstrate that monitoring the response of a patient to therapy regimens is feasible. Our work provides new opportunities for tracking cancer development.

• Item Type: Articles
• Additional Information: We would like to acknowledge the Wellcome Trust for support under grant numbers 098051 and 097678. A.F. is in part supported by the German Research Foundation (DFG) under grant number FI 1882/1-1. C.I. is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society under grant number 101239/Z/13/Z.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Illingworth, Dr Chris
• Authors: Fischer, A., Vázquez-García, I., Illingworth, C. J.R., and Mustonen, V.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Cell Reports
• Publisher: Elsevier (Cell Press)
• ISSN: 2211-1247
• ISSN (Online): 2211-1247
• Published Online: 29 May 2014
• Copyright Holders: Copyright © 2014 The Authors
• First Published: First published in Cell Reports 7(5):1740-1752
• Publisher Policy: Reproduced under a Creative Commons License