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Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing
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. H...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058534/ https://www.ncbi.nlm.nih.gov/pubmed/32025003 http://dx.doi.org/10.1038/s41588-019-0576-7 |
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author | Cortés-Ciriano, Isidro Lee, Jake June-Koo Xi, Ruibin Jain, Dhawal Jung, Youngsook L. Yang, Lixing Gordenin, Dmitry Klimczak, Leszek J. Zhang, Cheng-Zhong Pellman, David S. Park, Peter J. |
author_facet | Cortés-Ciriano, Isidro Lee, Jake June-Koo Xi, Ruibin Jain, Dhawal Jung, Youngsook L. Yang, Lixing Gordenin, Dmitry Klimczak, Leszek J. Zhang, Cheng-Zhong Pellman, David S. Park, Peter J. |
author_sort | Cortés-Ciriano, Isidro |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7058534 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-70585342020-03-18 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 Klimczak, Leszek J. Zhang, Cheng-Zhong Pellman, David S. Park, Peter J. Nat Genet Analysis 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. Nature Publishing Group US 2020-02-05 2020 /pmc/articles/PMC7058534/ /pubmed/32025003 http://dx.doi.org/10.1038/s41588-019-0576-7 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Analysis Cortés-Ciriano, Isidro Lee, Jake June-Koo Xi, Ruibin Jain, Dhawal Jung, Youngsook L. Yang, Lixing Gordenin, Dmitry Klimczak, Leszek J. Zhang, Cheng-Zhong Pellman, David S. Park, Peter J. Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing |
title | Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing |
title_full | Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing |
title_fullStr | Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing |
title_full_unstemmed | Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing |
title_short | Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing |
title_sort | comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing |
topic | Analysis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058534/ https://www.ncbi.nlm.nih.gov/pubmed/32025003 http://dx.doi.org/10.1038/s41588-019-0576-7 |
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