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Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Cortés-Ciriano, Isidro; Lee, Jake June-Koo; Xi, Ruibin; Jain, Dhawal; Jung, Youngsook L; Yang, Lixing; Gordenin, Dmitry; ... Park, Peter J; + view all (2020) Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing. Nature Genetics , 52 (3) pp. 331-341. 10.1038/s41588-019-0576-7. Green open access

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Abstract

Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer.

Type: Article
Title: Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41588-019-0576-7
Publisher version: https://doi.org/10.1038/s41588-019-0576-7
Language: English
Additional information: © 2022 Springer Nature Limited. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
Keywords: Cancer, Computational biology and bioinformatics, Genomics
UCL classification: 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 > Div of Surgery and Interventional Sci > Department of Targeted Intervention
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
URI: https://discovery.ucl.ac.uk/id/eprint/10148068
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