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

Autor: 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., Akdemir, Kadir C., Alvarez, Eva G., Baez-Ortega, Adrian, Beroukhim, Rameen, Boutros, Paul C., Bowtell, David D.L., Brors, Benedikt, Burns, Kathleen H., Campbell, Peter J., Chan, Kin, Chen, Ken, Dueso-Barroso, Ana, Dunford, Andrew J., Edwards, Paul A., Estivill, Xavier, Etemadmoghadam, Dariush, Feuerbach, Lars, Fink, J. Lynn, Frenkel-Morgenstern, Milana, Garsed, Dale W., Gerstein, Mark, Gordenin, Dmitry A., Haan, David, Haber, James E., Hess, Julian M., Hutter, Barbara, Imielinski, Marcin, Jones, David T.W., Ju, Young Seok, Kazanov, Marat D., Koh, Youngil, Korbel, Jan O., Kumar, Kiran, Lee, Eunjung Alice, Li, Yilong, Sidiropoulos, Nikos, Weischenfeldt, Joachim
Přispěvatelé: University of St Andrews. School of Medicine, University of St Andrews. Statistics, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Cellular Medicine Division, Cortés-Ciriano, Isidro [0000-0002-2036-494X], Lee, Jake June-Koo [0000-0003-1348-4094], Xi, Ruibin [0000-0001-7545-7361], Gordenin, Dmitry [0000-0002-8399-1836], Klimczak, Leszek J [0000-0003-3048-2576], Zhang, Cheng-Zhong [0000-0001-8825-7158], Park, Peter J [0000-0001-9378-960X], Apollo - University of Cambridge Repository
Rok vydání: 2020
Předmět:
Genome
Medical and Health Sciences
0302 clinical medicine
Neoplasms
2.1 Biological and endogenous factors
Aetiology
Càncer
Cancer
0303 health sciences
Chromothripsis
Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17]
Genomics
3rd-DAS
Biological Sciences
3. Good health
Women's cancers Radboud Institute for Health Sciences [Radboudumc 17]
030220 oncology & carcinogenesis
PCAWG Structural Variation Working Group
Human
Genome evolution
Evolution
Sequencing data
Computational biology
QH426 Genetics
Biology
Evolution
Molecular
RC0254
03 medical and health sciences
SDG 3 - Good Health and Well-being
medicine
Genetics
Humans
Gene
QH426
030304 developmental biology
Whole genome sequencing
Cromotripsis
Whole Genome Sequencing
Genome
Human
RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Human Genome
PCAWG Consortium
Molecular
medicine.disease
Human genetics
Computational biology and bioinformatics
Genòmica
Good Health and Well Being
Mutation
Genètica
Analysis
Human cancer
Developmental Biology
Zdroj: Nature Genetics, 52, 331-341
Nature Genetics, 52, 3, pp. 331-341
bioRxiv
Nature genetics, vol 52, iss 3
Cortés-Ciriano, I, Lee, J J K, Xi, R, Jain, D, Jung, Y L, Yang, L, Gordenin, D, Klimczak, L J, Zhang, C Z, Pellman, D S, Akdemir, K C, Alvarez, E G, Baez-Ortega, A, Beroukhim, R, Boutros, P C, Bowtell, D D L, Brors, B, Burns, K H, Campbell, P J, Chan, K, Chen, K, Cortés-Ciriano, I, Dueso-Barroso, A, Dunford, A J, Edwards, P A, Estivill, X, Etemadmoghadam, D, Feuerbach, L, Fink, J L, Frenkel-Morgenstern, M, Garsed, D W, Gerstein, M, Gordenin, D A, Haan, D, Haber, J E, Hess, J M, Hutter, B, Imielinski, M, Jones, D T W, Ju, Y S, Kazanov, M D, Klimczak, L J, Koh, Y, Korbel, J O, Kumar, K, Lee, E A, Lee, J J K, Li, Y, Sidiropoulos, N, Weischenfeldt, J, PCAWG Structural Variation Working Group & PCAWG Consortium 2020, ' Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing ', Nature Genetics . https://doi.org/10.1038/s41588-019-0576-7
Nature Genetics
ISSN: 1061-4036
Popis: 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.
Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.
Databáze: OpenAIRE
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