Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing
Creators: name: Xi, Ruibin
name: Jain, Dhawal
name: Jung, Youngsook L.
name: Yang, Lixing
name: Gordenin, Dmitry
name: Pellman, David S.
name: Akdemir, Kadir C.
name: Alvarez, Eva G.
name: Baez-Ortega, Adrian
name: Beroukhim, Rameen
name: Boutros, Paul C.
name: Bowtell, David D. L.
name: Brors, Benedikt
name: Burns, Kathleen H.
name: Campbell, Peter J.
name: Chan, Kin
name: Chen, Ken
name: Cortés-Ciriano, Isidro
name: Dueso-Barroso, Ana
name: Dunford, Andrew J.
name: Edwards, Paul A.
name: Estivill, Xavier
name: Etemadmoghadam, Dariush
name: Feuerbach, Lars
name: Fink, J. Lynn
name: Frenkel-Morgenstern, Milana
name: Garsed, Dale W.
name: Gerstein, Mark
name: Gordenin, Dmitry A.
name: Haan, David
name: Haber, James E.
name: Hess, Julian M.
name: Hutter, Barbara
name: Imielinski, Marcin
name: Jones, David T. W.
name: Ju, Young Seok
name: Kazanov, Marat D.
name: Klimczak, Leszek J.
name: Koh, Youngil
name: Korbel, Jan O.
name: Kumar, Kiran
name: Lee, Eunjung Alice
name: Lee, Jake June-Koo
name: Li, Yilong
name: Lynch, Andy G.
name: Macintyre, Geoff
name: Markowetz, Florian
name: Martincorena, Iñigo
name: Martinez-Fundichely, Alexander
name: Miyano, Satoru
name: Nakagawa, Hidewaki
name: Navarro, Fabio C. P.
name: Ossowski, Stephan
name: Park, Peter J.
name: Pearson, John V.
name: Puiggròs, Montserrat
name: Rippe, Karsten
name: Roberts, Nicola D.
name: Roberts, Steven A.
name: Rodriguez-Martin, Bernardo
name: Schumacher, Steven E.
name: Scully, Ralph
name: Shackleton, Mark
name: Sidiropoulos, Nikos
name: Sieverling, Lina
name: Stewart, Chip
name: Torrents, David
name: Tubio, Jose M. C.
name: Villasante, Izar
name: Waddell, Nicola
name: Wala, Jeremiah A.
name: Weischenfeldt, Joachim
name: Yao, Xiaotong
name: Yoon, Sung-Soo
name: Zamora, Jorge
name: Zhang, Cheng-Zhong
Publisher: name: Apollo - University of Cambridge Repository
Year: 2020
Subjects: Analysis
/631/67
/631/114
/631/208/212
/45
/45/23
analysis

description: Funder: Ludwig Center at Harvard
description: Funder: National Cancer Institute: K22CA193848
description: Funder: US National Institutes of Health Intramural Research Program Project Z1AES103266
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.