@article{7a9a3e378d58428cacca8f57bce882fe,
title = "Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing",
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.",
keywords = "Cancer, Computational biology and bioinformatics, Genomics",
author = "Isidro Cort{\'e}s-Ciriano and Lee, {Jake June-Koo} and Ruibin Xi and Dhawal Jain and Jung, {Youngsook L.} and Lixing Yang and Dmitry Gordenin and Klimczak, {Leszek J.} and Cheng-Zhong Zhang and Pellman, {David S.} and {PCAWG Structural Variation Working Group} and Park, {Peter J.} and {PCAWG Consortium} and Akdemir, {Kadir C.} and Alvarez, {Eva G.} and Adrian Baez-Ortega and Rameen Beroukhim and Boutros, {Paul C.} and Bowtell, {David D.L.} and Benedikt Brors and Burns, {Kathleen H.} and Campbell, {Peter J.} and Kin Chan and Ken Chen and Isidro Cort{\'e}s-Ciriano and Ana Dueso-Barroso and Dunford, {Andrew J.} and Edwards, {Paul A.} and Xavier Estivill and Dariush Etemadmoghadam and Lars Feuerbach and Fink, {J. Lynn} and Milana Frenkel-Morgenstern and Garsed, {Dale W.} and Mark Gerstein and Gordenin, {Dmitry A.} and David Haan and Haber, {James E.} and Hess, {Julian M.} and Barbara Hutter and Marcin Imielinski and Jones, {David T.W.} and Ju, {Young Seok} and Kazanov, {Marat D.} and Klimczak, {Leszek J.} and Youngil Koh and Korbel, {Jan O.} and Kiran Kumar and Lee, {Eunjung Alice} and Lee, {Jake June Koo} and Yilong Li and Geoff Macintyre and Lynch, {Andy G.}",
note = "This work was supported by the European Union{\textquoteright}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.). We thank the Research Information Technology Group at Harvard Medical School for providing computational resources and S. Ouellette in the Park laboratory for help in deploying the companion website. We acknowledge the contributions of the many clinical networks across ICGC and TCGA, who provided samples and data to the PCAWG Consortium, and the contributions of the Technical Working Group and the Germline Working Group of the PCAWG Consortium for collation, realignment and harmonized variant calling of the cancer genomes used in this study. We thank the patients and their families for their participation in the individual ICGC and TCGA projects.",
year = "2020",
month = mar,
doi = "10.1038/s41588-019-0576-7",
language = "English",
volume = "52",
pages = "331--341",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature publishing group",
number = "3",
}
