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000153754 1001_ $$00000-0002-2036-494X$$aCortés-Ciriano, Isidro$$b0
000153754 245__ $$aComprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing.
000153754 260__ $$aLondon$$bMacmillan Publishers Limited, part of Springer Nature$$c2020
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000153754 500__ $$a2020 Mar;52(3):331-341 / In the version of this article initially published, author Peter J. Park had affiliation numbers 2 and 3; the correct affiliation numbers are1 and 2. The error has been corrected in the HTML and PDF versions of the article.
000153754 520__ $$aChromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer.
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000153754 7001_ $$00000-0003-1348-4094$$aLee, Jake June-Koo$$b1
000153754 7001_ $$00000-0001-7545-7361$$aXi, Ruibin$$b2
000153754 7001_ $$aJain, Dhawal$$b3
000153754 7001_ $$aJung, Youngsook L$$b4
000153754 7001_ $$aYang, Lixing$$b5
000153754 7001_ $$00000-0002-8399-1836$$aGordenin, Dmitry$$b6
000153754 7001_ $$00000-0003-3048-2576$$aKlimczak, Leszek J$$b7
000153754 7001_ $$aZhang, Cheng-Zhong$$b8
000153754 7001_ $$aPellman, David S$$b9
000153754 7001_ $$aGroup, PCAWG Structural Variation Working$$b10$$eCollaboration Author
000153754 7001_ $$00000-0001-9378-960X$$aPark, Peter J$$b11
000153754 7001_ $$aConsortium, PCAWG$$b12$$eCollaboration Author
000153754 7001_ $$aAkdemir, Kadir C$$b13
000153754 7001_ $$aAlvarez, Eva G$$b14
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000153754 7001_ $$aKlimczak, Leszek J$$b44
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