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Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes.

Dentro, SC; Leshchiner, I; Haase, K; Tarabichi, M; Wintersinger, J; Deshwar, AG; Yu, K; ... PCAWG Evolution and Heterogeneity Working Group and the PCAWG Co, .; + view all (2021) Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes. Cell , 184 (8) pp. 2239-2254. 10.1016/j.cell.2021.03.009. Green open access

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Abstract

Intra-tumor heterogeneity (ITH) is a mechanism of therapeutic resistance and therefore an important clinical challenge. However, the extent, origin, and drivers of ITH across cancer types are poorly understood. To address this, we extensively characterize ITH across whole-genome sequences of 2,658 cancer samples spanning 38 cancer types. Nearly all informative samples (95.1%) contain evidence of distinct subclonal expansions with frequent branching relationships between subclones. We observe positive selection of subclonal driver mutations across most cancer types and identify cancer type-specific subclonal patterns of driver gene mutations, fusions, structural variants, and copy number alterations as well as dynamic changes in mutational processes between subclonal expansions. Our results underline the importance of ITH and its drivers in tumor evolution and provide a pan-cancer resource of comprehensively annotated subclonal events from whole-genome sequencing data.

Type: Article
Title: Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cell.2021.03.009
Publisher version: https://doi.org/10.1016/j.cell.2021.03.009
Language: English
Additional information: Copyright 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: branching evolution, cancer driver genes, cancer evolution, intra-tumor heterogeneity, pan-cancer genomics, subclonal reconstruction, tumor phylogeny, whole-genome sequencing
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/10126268
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