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

Mostra el registre complet Registre parcial de l'ítem

• dc.contributor.author Cortés-Ciriano, Isidro
• dc.contributor.author Lee, Jake June-Koo
• dc.contributor.author Xi, Ruibin
• dc.contributor.author Jain, Dhawal
• dc.contributor.author Jung, Youngsook L.
• dc.contributor.author Yang, Lixing
• dc.contributor.author Gordenin, Dmitry
• dc.contributor.author Klimczak, Leszek J.
• dc.contributor.author Zhang, Cheng-Zhong
• dc.contributor.author Pellman, David S.
• dc.contributor.author PCAWG Structural Variation Working Group
• dc.contributor.author Park, Peter J.
• dc.contributor.author PCAWG Consortium
• dc.contributor.author Ossowski, Stephan
• dc.contributor.author Pearson, John V.
• dc.date.accessioned 2020-04-24T07:19:15Z
• dc.date.available 2020-04-24T07:19:15Z
• dc.date.issued 2020
• dc.description.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.
• dc.description.sponsorship This work was supported by the European Union’s Framework Programme For Research and Innovation Horizon 2020 under the Marie Sklodowska-Curie grant agreement no. 703543 (I.C.-C.), the Ludwig Center at Harvard (I.C.-C., J.J.-K.L. and P.J.P.), K22CA193848 (L.Y.), R01CA213404 (D.S.P.) and the US National Institutes of Health Intramural Research Program Project Z1AES103266 (D.G. and L.J.K.)
• dc.format.mimetype application/pdf
• dc.identifier.citation Cortés-Ciriano I, Lee JJ, Xi R, Jain D, Jung YL, Yang L et al. Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing. Nat Genet. 2020 Mar; 52(3): 331-341. DOI: 10.1038/s41588-019-0576-7
• dc.identifier.doi http://dx.doi.org/10.1038/s41588-019-0576-7
• dc.identifier.issn 1061-4036
• dc.identifier.uri http://hdl.handle.net/10230/44324
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Nature Genetics. 2020 Mar;52(3):331-41
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/703543
• dc.rights © 2020 Isidro Cortés-Ciriano et al. 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
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other Cromotripsis
• dc.subject.other Càncer
• dc.subject.other Genòmica
• dc.subject.other Genètica
• dc.title Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion