Massive genomic rearrangement acquired in a single catastrophic event during cancer development
Open accessAbstract
Cancer is driven by somatically acquired point mutations and chromosomal rearrangements, conventionally thought to accumulate gradually over time. Using next-generation sequencing, we characterize a phenomenon, which we term chromothripsis, whereby tens to hundreds of genomic rearrangements occur in a one-off cellular crisis. Rearrangements involving one or a few chromosomes crisscross back and forth across involved regions, generating frequent oscillations between two copy number states. These genomic hallmarks are highly improbable if rearrangements accumulate over time and instead imply that nearly all occur during a single cellular catastrophe. The stamp of chromothripsis can be seen in at least 2%-3% of all cancers, across many subtypes, and is present in ∼25% of bone cancers. We find that one, or indeed more than one, cancer-causing lesion can emerge out of the genomic crisis. This phenomenon has important implications for the origins of genomic remodeling and temporal emergence of cancer.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
These rearrangement patterns have been reported in breast cancer but not associated with germline predisposition.
“Whilst these patterns of rearrangements have been reported in BC [28, 29], they have not been associated with a germline predisposition.”
From Whole-genome sequencing reveals clinically relevant insights into the aetiology of familial breast cancers (2019) · cites this paper as [28]
SNU-C1 cells contain a complex rearrangement (chromothripsis) across the entire chromosome 15.
“SNU-C1 cells contain a complex rearrangement (chromothripsis) across the entire chromosome 15, which was reported by WGS and spectral karyotyping41.”
From Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer (2020) · cites this paper as [41]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Circos: An information aesthetic for comparative genomicsPreprint
Krzywinski, M. I., Schein, J. E., Birol, İ., Connors, J. M., Gascoyne, R. D., Horsman, D. E., Jones, S. J. M., & Marra, M. A. (2009) · Genome Research · doi:10.1101/gr.092759.109 · Cited by 10,838 · see citing works
The landscape of somatic copy-number alteration across human cancers
Beroukhim, R., Mermel, C. H., Porter, D., Wei, G., Raychaudhuri, S., Donovan, J., Barretina, J., Boehm, J. S., Dobson, J., Urashima, M., et al. (2010) · Nature · doi:10.1038/nature08822 · Cited by 4,017 · see citing works
miR-15 and miR-16 induce apoptosis by targeting BCL2
Cimmino, A., Calin, G. A., Fabbri, M., Iorio, M. V., Ferracin, M., Shimizu, M., Wojcik, S. E., Aqeilan, R. I., Zupo, S., Dono, M., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506654102 · Cited by 3,510 · see citing works
Stratton, M. R., Campbell, P. J., & Futreal, P. A. (2009) · Nature · doi:10.1038/nature07943 · Cited by 3,459 · see citing works
Self-citationMapping short DNA sequencing reads and calling variants using mapping quality scores
Li, H., Ruan, J., & Durbin, R. (2008) · Genome Research · doi:10.1101/gr.078212.108 · Cited by 2,638 · see citing works
Recurring mutations found by sequencing an acute myeloid leukemia genome
Mardis, E. R., Ding, L., Dooling, D. J., Larson, D. E., McLellan, M. D., Chen, K., Koboldt, D. C., Fulton, R. S., Delehaunty, K. D., McGrath, S. D., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0903840 · Cited by 2,219 · see citing works
A comprehensive catalogue of somatic mutations from a human cancer genome
Pleasance, E. D., Cheetham, R. K., Stephens, P. J., McBride, D. J., Humphray, S. J., Greenman, C. D., Varela, I., Lin, M.-L., Ordóñez, G. R., Bignell, G. R., et al. (2010) · Nature · doi:10.1038/nature08658 · Cited by 1,696 · see citing works
Self-citationTHE STABILITY OF BROKEN ENDS OF CHROMOSOMES IN ZEA MAYS
McClintock, B. (1941) · Genetics · doi:10.1093/genetics/26.2.234 · Cited by 1,610 · see citing works
Emergence and pandemic potential of swine-origin H1N1 influenza virus
Neumann, G., Noda, T., & Kawaoka, Y. (2009) · Nature · doi:10.1038/nature08157 · Cited by 1,562 · see citing works
The patterns and dynamics of genomic instability in metastatic pancreatic cancer
Campbell, P. J., Yachida, S., Mudie, L. J., Stephens, P. J., Pleasance, E. D., Stebbings, L. A., Morsberger, L. A., Latimer, C., McLaren, S., Lin, M.-L., et al. (2010) · Nature · doi:10.1038/nature09460 · Cited by 1,317 · see citing works
Self-citationSystematic sequencing of renal carcinoma reveals inactivation of histone modifying genes
Dalgliesh, G. L., Furge, K., Greenman, C., Chen, L., Bignell, G., Butler, A., Davies, H., Edkins, S., Hardy, C., Latimer, C., et al. (2010) · Nature · doi:10.1038/nature08672 · Cited by 1,173 · cited 1× · see citing works
“WRN is a cancer gene in which germlinemutation causesWerner syndrome, a condition associated with markedly increased risk of bone tumors, and in which somatic inactivating mutations have been documented in renal cancer (Dalgliesh et al., 2010).”
BackgroundSelf-citationPancreatic cancer biology and genetics
Bardeesy, N. M., & DePinho, R. A. (2002) · Nature reviews. Cancer · doi:10.1038/nrc949 · Cited by 1,144 · see citing works
Beyond the Sequence: Cellular Organization of Genome Function
Misteli, T. (2007) · Cell · doi:10.1016/j.cell.2007.01.028 · Cited by 1,140 · see citing works
Genome remodelling in a basal-like breast cancer metastasis and xenograft
Ding, L., Ellis, M. J., Li, S., Larson, D. E., Chen, K., Wallis, J. W., Harris, C. C., McLellan, M. D., Fulton, R. S., Fulton, L., et al. (2010) · Nature · doi:10.1038/nature08989 · Cited by 1,134 · see citing works
Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice
Artandi, S. E., Chang, S., Lee, S.-L., Alson, S., Gottlieb, G. J., Chin, L., & DePinho, R. A. (2000) · Nature · doi:10.1038/35020592 · Cited by 1,085 · see citing works
A small-cell lung cancer genome with complex signatures of tobacco exposure
Pleasance, E., Stephens, P. J., O’Meara, S., McBride, D. J., Meynert, A. M., Jones, D., Lin, M., Beare, D. M., Lau, K. W., Greenman, C., et al. (2009) · Nature · doi:10.1038/nature08629 · Cited by 1,067 · see citing works
Self-citationMutational evolution in a lobular breast tumour profiled at single nucleotide resolution
Shah, S. P., Morin, R. D., Khattra, J. S., Prentice, L., Pugh, T. J., Burleigh, A., Delaney, A. D., Gelmon, K. A., Guliany, R., Senz, J., et al. (2009) · Nature · doi:10.1038/nature08489 · Cited by 1,063 · see citing works
Complex landscapes of somatic rearrangement in human breast cancer genomes
Stephens, P. J., McBride, D. J., Lin, M., Varela, I., Pleasance, E., Simpson, J. T., Stebbings, L. A., Leroy, C., Edkins, S., Mudie, L. J., et al. (2009) · Nature · doi:10.1038/nature08645 · Cited by 833 · see citing works
Self-citationComparative lesion sequencing provides insights into tumor evolution
Jones, S., Chen, W.-D. D., Parmigiani, G., Diehl, F., Beerenwinkel, N., Tibor Antal, A., Traulsen, A., Nowak, M. A., Siegel, C., Velculescu, V. E., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712345105 · Cited by 817 · see citing works
Campbell, P. J., Stephens, P. J., Pleasance, E., O’Meara, S., Li, H., Santarius, T., Stebbings, L. A., Leroy, C., Edkins, S., Hardy, C. W., et al. (2008) · Nature Genetics · doi:10.1038/ng.128 · Cited by 812 · see citing works
Self-citationLinking functional decline of telomeres, mitochondria and stem cells during ageing
Sahin, E., & DePinho, R. A. (2010) · Nature · doi:10.1038/nature08982 · Cited by 759 · see citing works
A large genome center's improvements to the Illumina sequencing system
Quail, M. A., Kozarewa, I., Smith, F., Scally, A., Stephens, P. J., Durbin, R. M., Swerdlow, H., & Turner, D. (2008) · Nature Methods · doi:10.1038/nmeth.1270 · Cited by 732 · see citing works
Self-citationSignatures of mutation and selection in the cancer genome
Bignell, G. R., Greenman, C. D., Davies, H., Butler, A. P., Edkins, S., Andrews, J. M., Buck, G., Chen, L., Beare, D., Latimer, C., et al. (2010) · Nature · doi:10.1038/nature08768 · Cited by 707 · see citing works
Self-citationFBXW7/hCDC4 Is a General Tumor Suppressor in Human Cancer
Akhoondi, S., Sun, D., von der Lehr, N., Apostolidou, S., Klotz, K., Malyukova, A., Cepeda, D., Fiegl, H., Dafou, D., Marth, C., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-1320 · Cited by 507 · see citing works
Sher, T., Dy, G. K., & Adjei, A. A. (2008) · Mayo Clinic Proceedings · doi:10.4065/83.3.355 · Cited by 502 · see citing works
Gisselsson, D., Jonson, T., Petersén, Å., Strömbeck, B., Cin, P. D., Höglund, M., Mitelman, F., Mertens, F., & Mandahl, N. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.211357798 · Cited by 416 · see citing works
Fbxw7/Cdc4 is a p53-dependent, haploinsufficient tumour suppressor gene
Mao, J.-H., Perez-losada, J., Wu, D., DelRosario, R., Tsunematsu, R., Nakayama, K. I., Brown, K., Bryson, S., & Balmain, A. (2004) · Nature · doi:10.1038/nature03155 · Cited by 390 · see citing works
Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers
Maser, R. S., Choudhury, B., Campbell, P. J., Feng, B., Wong, K.-K., Protopopov, A., O’Neil, J., Gutierrez, A., Ivanova, E., Perna, I., et al. (2007) · Nature · doi:10.1038/nature05886 · Cited by 377 · see citing works
Self-citationTelomere dysfunction provokes regional amplification and deletion in cancer genomes
O'Hagan, R. C., Chang, S., Maser, R. S., Mohan, R., Artandi, S. E., Chin, L., & DePinho, R. A. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00094-6 · Cited by 246 · see citing works
PICNIC: an algorithm to predict absolute allelic copy number variation with microarray cancer data
Greenman, C., Bignell, G. R., Butler, A. P., Edkins, S., Hinton, J., Beare, D. M., Swamy, S., Santarius, T., Chen, L., Widaa, S., et al. (2009) · Biostatistics · doi:10.1093/biostatistics/kxp045 · Cited by 196 · see citing works
Self-citationBignell, G. R., Santarius, T., Pole, J. C. M., Butler, A. P., Perry, J., Pleasance, E., Greenman, C., Menzies, A. H., Taylor, S., Edkins, S., et al. (2007) · Genome Research · doi:10.1101/gr.6522707 · Cited by 195 · see citing works
Self-citationKemp, Z., Rowan, A., Chambers, W. M., Wortham, N. C., Halford, S. E. R., Sieber, O. M., Mortensen, N., Herbay, A. V., Gunther, T., Ilyas, M., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-2565 · Cited by 89 · see citing works
Wang, J., Hagman, K. D. F., Scaringe, W. A., Tsai, K., Liu, N., Gu, D., Li, W., Hill, K. A., & Sommer, S. S. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610902104 · Cited by 74 · see citing works
Pampalona, J., Soler, D., Genescà, A., & Tusell, L. (2009) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2009.10.001 · Cited by 69 · see citing works
Multiplex-fluorescence in situ hybridization for chromosome karyotyping
Geigl, J. B., Uhrig, S., & Speicher, M. R. (2006) · Nature Protocols · doi:10.1038/nprot.2006.160 · Cited by 49 · see citing works
Chen, J., Férec, C., & Cooper, D. N. (2009) · Human Mutation · doi:10.1002/humu.21088 · Cited by 49 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The cancer genome atlas pan-cancer analysis project
The Cancer Genome Atlas Research Network, Weinstein, J. N., Collisson, E. A., Mills, G. B., Shaw, K. R. M., Ozenberger, B. A., Ellrott, K., Shmulevich, I., Sander, C., & Stuart, J. M. (2013) · Nature Genetics · doi:10.1038/ng.2764 · Cited by 9,092 · see citing works
Comprehensive molecular profiling of lung adenocarcinoma
The Cancer Genome Atlas Research Network (2014) · Nature · doi:10.1038/nature13385 · Cited by 5,732 · see citing works
Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia
The Cancer Genome Atlas Research Network (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1301689 · Cited by 5,078 · see citing works
The repertoire of mutational signatures in human cancer
Alexandrov, L. B., Kim, J., Haradhvala, N. J., Huang, M. N., Tian Ng, A. W., Wu, Y., Boot, A., Covington, K. R., Gordenin, D. A., Bergstrom, E. N., et al. (2020) · Nature · doi:10.1038/s41586-020-1943-3 · Cited by 3,496 · see citing works
Self-citationPan-cancer analysis of whole genomes
The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium, Aaltonen, L. A., Abascal, F., Abeshouse, A., Aburatani, H., Adams, D. J., Agrawal, N., Ahn, K. S., Ahn, S.-M., Aikata, H., et al. (2020) · Nature · doi:10.1038/s41586-020-1969-6 · Cited by 3,064 · see citing works
Self-citationGreaves, M., & Maley, C. C. (2012) · Nature · doi:10.1038/nature10762 · Cited by 3,162 · see citing works
A view on drug resistance in cancer
Vasan, N., Baselga, J., & Hyman, D. M. (2019) · Nature · doi:10.1038/s41586-019-1730-1 · Cited by 2,770 · see citing works
Whole genomes redefine the mutational landscape of pancreatic cancer
Initiative, A. P. C. G., Waddell, N., Pajic, M., Patch, A.-M., Chang, D. K., Kassahn, K. S., Bailey, P., Johns, A. L., Miller, D., Nones, K., et al. (2015) · Nature · doi:10.1038/nature14169 · Cited by 2,642 · see citing works
“The majority of structural variants were intra-chromosomal (10,114) and were classified into 7 types: intra-chromosomal rearrangements (5,860), deletions (1,393), duplications (128), tandem duplications (179), inversions (1,629), foldback inversions (579) and amplified inversions (346); inter-chromosomal translocation…”
BackgroundSelf-citationMutational Processes Molding the Genomes of 21 Breast Cancers
Nik-Zainal, S., Alexandrov, L. B., Wedge, D. C., Van Loo, P., Greenman, C. D., Raine, K., Jones, D., Hinton, J., Marshall, J., Stebbings, L. A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.024 · Cited by 1,909 · see citing works
Self-citationThe genetic basis of early T-cell precursor acute lymphoblastic leukaemia
Zhang, J., Ding, L., Holmfeldt, L., Wu, G., Heatley, S. L., Payne-Turner, D., Easton, J., Chen, X., Wang, J., Rusch, M., et al. (2012) · Nature · doi:10.1038/nature10725 · Cited by 1,596 · see citing works
“Three cases (SJTALL001, SJTALL002, SJTALL003) had multiple complex rearrangements with breakpoints suggestive of a single cellular catastrophe (“chromothripsis&rdquo”
BackgroundThe Life History of 21 Breast Cancers
Nik-Zainal, S., Van Loo, P., Wedge, D. C., Alexandrov, L. B., Greenman, C. D., Lau, K. W., Raine, K., Jones, D., Marshall, J., Ramakrishna, M., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.023 · Cited by 1,443 · see citing works
Self-citationSomatic mutation in cancer and normal cells
Martincorena, I., & Campbell, P. J. (2015) · Science · doi:10.1126/science.aab4082 · Cited by 1,396 · see citing works
Self-citationTranslational biology of osteosarcoma
Kansara, M., Teng, M. W., Smyth, M. J., & Thomas, D. M. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3838 · Cited by 1,294 · see citing works
DNA breaks and chromosome pulverization from errors in mitosis
Crasta, K., Ganem, N. J., Dagher, R., Lantermann, A. B., Ivanova, E. V., Pan, Y., Nezi, L., Protopopov, A., Chowdhury, D., & Pellman, D. (2012) · Nature · doi:10.1038/nature10802 · Cited by 1,227 · see citing works
Genome-Wide Detection of Single-Nucleotide and Copy-Number Variations of a Single Human Cell
Zong, C., Lu, S., Chapman, A. R., & Xie, X. S. (2012) · Science · doi:10.1126/science.1229164 · Cited by 1,154 · see citing works
Biological and therapeutic impact of intratumor heterogeneity in cancer evolution
McGranahan, N., & Swanton, C. (2015) · Cancer Cell · doi:10.1016/j.ccell.2014.12.001 · Cited by 1,077 · see citing works
Clonal evolution in breast cancer revealed by single nucleus genome sequencing
Wang, Y., Waters, J., Leung, M. L., Unruh, A., Roh, W., Shi, X., Chen, K., Scheet, P., Vattathil, S., Liang, H., et al. (2014) · Nature · doi:10.1038/nature13600 · Cited by 1,029 · see citing works
Whole-genome landscape of pancreatic neuroendocrine tumours
Initiative, A. P. C. G., Scarpa, A., Chang, D. K., Nones, K., Corbo, V., Patch, A.-M., Bailey, P., Lawlor, R. T., Johns, A. L., Miller, D. K., et al. (2017) · Nature · doi:10.1038/nature21063 · Cited by 999 · see citing works
ATR prohibits replication catastrophe by preventing global exhaustion of RPA
Toledo, L. I., Altmeyer, M., Rask, M.-B., Lukas, C., Larsen, D. H., Povlsen, L. K., Bekker-Jensen, S., Mailand, N., Bartek, J., & Lukas, J. (2013) · Cell · doi:10.1016/j.cell.2013.10.043 · Cited by 911 · see citing works
Advancing therapy for osteosarcoma
Gill, J., & Gorlick, R. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00519-8 · Cited by 876 · see citing works
Rausch, T., Jones, D. T. W., Zapatka, M., Stütz, A. M., Zichner, T., Weischenfeldt, J., Jäger, N., Remke, M., Shih, D., Northcott, P. A., et al. (2012) · Cell · doi:10.1016/j.cell.2011.12.013 · Cited by 865 · see citing works
Dissecting the genomic complexity underlying medulloblastoma
Jones, D. T. W., Jäger, N., Kool, M., Zichner, T., Hutter, B., Sultan, M., Cho, Y.-J., Pugh, T. J., Hovestadt, V., Stütz, A. M., et al. (2012) · Nature · doi:10.1038/nature11284 · Cited by 839 · see citing works
Heterogeneity of genomic evolution and mutational profiles in multiple myeloma
Bolli, N., Avet-Loiseau, H., Wedge, D. C., Van Loo, P., Alexandrov, L. B., Martincorena, I., Dawson, K. J., Iorio, F., Nik-Zainal, S., Bignell, G. R., et al. (2014) · Nature Communications · doi:10.1038/ncomms3997 · Cited by 875 · see citing works
Self-citationCatastrophic nuclear envelope collapse in cancer cell micronuclei
Hatch, E. M., Fischer, A. H., Deerinck, T. J., & Hetzer, M. W. (2013) · Cell · doi:10.1016/j.cell.2013.06.007 · Cited by 741 · see citing works
Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing
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., et al. (2020) · Nature Genetics · doi:10.1038/s41588-019-0576-7 · Cited by 712 · see citing works
Self-citationTelomeres in cancer: tumour suppression and genome instability
Maciejowski, J., & de Lange, T. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.171 · Cited by 745 · see citing works
Recurrent Somatic Structural Variations Contribute to Tumorigenesis in Pediatric Osteosarcoma
Chen, X., Bahrami, A., Pappo, A., Easton, J., Dalton, J., Hedlund, E., Ellison, D., Shurtleff, S., Wu, G., Wei, L., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.03.003 · Cited by 752 · see citing works
Melanoma genome sequencing reveals frequent PREX2 mutations
Berger, M. F., Hodis, E., Heffernan, T. P., Deribe, Y. L., Lawrence, M. S., Protopopov, A., Ivanova, E., Watson, I. R., Nickerson, E., Ghosh, P., et al. (2012) · Nature · doi:10.1038/nature11071 · Cited by 756 · see citing works
Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer
Quigley, D. A., Dang, H. X., Zhao, S. G., Lloyd, P., Aggarwal, R., Alumkal, J. J., Foye, A., Kothari, V., Perry, M. D., Bailey, A. M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.06.039 · Cited by 733 · see citing works
Chromothripsis and Kataegis Induced by Telomere Crisis
Maciejowski, J., Li, Y., Bosco, N., Campbell, P. J., & de Lange, T. (2015) · Cell · doi:10.1016/j.cell.2015.11.054 · Cited by 675 · see citing works
Self-citationNew Horizons in the Treatment of Osteosarcoma
Meltzer, P. S., & Helman, L. J. (2021) · New England Journal of Medicine · doi:10.1056/nejmra2103423 · Cited by 672 · see citing works
Tumour heterogeneity and metastasis at single-cell resolution
Lawson, D. A., Kessenbrock, K., Davis, R. T., Pervolarakis, N., & Werb, Z. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0236-7 · Cited by 606 · see citing works
Talkowski, M. E., Rosenfeld, J. A., Blumenthal, I., Pillalamarri, V., Chiang, C., Heilbut, A., Ernst, C., Hanscom, C., Rossin, E., Lindgren, A. M., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.028 · Cited by 577 · see citing works
Single-Cell Exome Sequencing and Monoclonal Evolution of a JAK2-Negative Myeloproliferative Neoplasm
Hou, Y., Song, L., Zhu, P., Zhang, B., Tao, Y., Xu, X., Li, F., Wu, K., Liang, J., Shao, D., et al. (2012) · Cell · doi:10.1016/j.cell.2012.02.028 · Cited by 541 · see citing works
A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns
Notta, F., Chan-Seng-Yue, M., Lemire, M., Li, Y., Wilson, G. W., Connor, A. A., Denroche, R. E., Liang, S.-B., Brown, A. M. K., Kim, J. C., et al. (2016) · Nature · doi:10.1038/nature19823 · Cited by 528 · see citing works
Self-citationPerry, J. A., Kiezun, A., Tonzi, P., Van Allen, E. M., Carter, S. L., Baca, S. C., Cowley, G. S., Bhatt, A. S., Rheinbay, E., Pedamallu, C. S., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1419260111 · Cited by 481 · see citing works
Genetics and Genetic Biomarkers in Sporadic Colorectal Cancer
Carethers, J. M., & Jung, B. H. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.06.047 · Cited by 483 · see citing works
Mechanisms generating cancer genome complexity from a single cell division error
Umbreit, N. T., Zhang, C.-Z., Lynch, L. D., Blaine, L. J., Cheng, A. M., Tourdot, R., Sun, L., Almubarak, H. F., Judge, K., Mitchell, T. J., et al. (2020) · Science · doi:10.1126/science.aba0712 · Cited by 439 · see citing works
Weischenfeldt, J., Dubash, T., Drainas, A. P., Mardin, B. R., Chen, Y., Stütz, A. M., Waszak, S. M., Bosco, G., Halvorsen, A. R., Raeder, B., et al. (2017) · Nature Genetics · doi:10.1038/ng.3722 · Cited by 404 · see citing works
Redin, C., Brand, H., Collins, R. L., Kammin, T., Mitchell, E., Hodge, J. C., Hanscom, C., Pillalamarri, V., Seabra, C. M., Abbott, M.-A., et al. (2017) · Nature Genetics · doi:10.1038/ng.3720 · Cited by 334 · see citing works
Gene Copy-Number Alterations: A Cost-Benefit Analysis
Tang, Y.-C., & Amon, A. (2013) · Cell · doi:10.1016/j.cell.2012.11.043 · Cited by 348 · see citing works
DNA double-strand break repair pathway choice and cancer
Aparicio, T., Baer, R., & Gautier, J. (2014) · DNA Repair · doi:10.1016/j.dnarep.2014.03.014 · Cited by 347 · see citing works
Nuclear envelope assembly defects link mitotic errors to chromothripsis
Liu, S., Kwon, M., Mannino, M., Yang, N., Renda, F., Khodjakov, A., & Pellman, D. (2018) · Nature · doi:10.1038/s41586-018-0534-z · Cited by 314 · see citing works
Watkins, J. A., Irshad, S., Grigoriadis, A., & Tutt, A. N. (2014) · Breast Cancer Research · doi:10.1186/bcr3670 · Cited by 327 · see citing works
Galanos, P., Vougas, K., Walter, D., Polyzos, A., Maya-Mendoza, A., Haagensen, E. J., Kokkalis, A., Roumelioti, F.-M., Gagos, S., Tzetis, M., et al. (2016) · Nature Cell Biology · doi:10.1038/ncb3378 · Cited by 308 · see citing works
Tang, H. L., Tang, H. M., Mak, K. H., Hu, S., Wang, S. S., Wong, K. M., Wong, C. S. T., Wu, H. Y., Law, H. T., Liu, K., et al. (2012) · Molecular Biology of the Cell · doi:10.1091/mbc.e11-11-0926 · Cited by 293 · see citing works
Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer
Akdemir, K. C., Le, V. T., Chandran, S., Li, Y., Verhaak, R. G., Beroukhim, R., Campbell, P. J., Chin, L., Dixon, J. R., Futreal, P. A., et al. (2020) · Nature Genetics · doi:10.1038/s41588-019-0564-y · Cited by 283 · see citing works
Self-citationThe prenatal origins of cancer
Marshall, G. M., Carter, D. R., Cheung, B. B., Liu, T., Mateos, M. K., Meyerowitz, J. G., & Weiss, W. A. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3679 · Cited by 281 · see citing works
Yachida, S., White, C. M., Naito, Y., Zhong, Y., Brosnan, J. A., Macgregor-Das, A. M., Morgan, R. A., Saunders, T., Laheru, D. A., Herman, J. M., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-1215 · Cited by 280 · see citing works
Self-citationMutational signatures of ionizing radiation in second malignancies
Behjati, S., Gundem, G., Wedge, D. C., Roberts, N. D., Tarpey, P. S., Cooke, S. L., Van Loo, P., Alexandrov, L. B., Ramakrishna, M., Davies, H., et al. (2016) · Nature Communications · doi:10.1038/ncomms12605 · Cited by 274 · see citing works
Self-citationKoirala, P., Roth, M. E., Gill, J., Piperdi, S., Chinai, J. M., Geller, D. S., Hoang, B. H., Park, A., Fremed, M. A., Zang, X., et al. (2016) · Scientific Reports · doi:10.1038/srep30093 · Cited by 267 · see citing works
Davoli, T., & de Lange, T. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.03.044 · Cited by 242 · see citing works
Tracing Oncogene Rearrangements in the Mutational History of Lung Adenocarcinoma
Lee, J. J.-K., Park, S., Park, H., Kim, S., Lee, J., Lee, J., Youk, J., Yi, K., An, Y., Park, I. K., et al. (2019) · Cell · doi:10.1016/j.cell.2019.05.013 · Cited by 233 · see citing works
Repair of DNA Double-Strand Breaks by the Nonhomologous End Joining Pathway
Stinson, B. M., & Loparo, J. J. (2021) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-080320-110356 · Cited by 223 · see citing works
The pancreatic cancer genome revisited
Hayashi, A., Hong, J., & Iacobuzio-Donahue, C. A. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00463-z · Cited by 211 · see citing works
Self-citationThe Architecture and Evolution of Cancer Neochromosomes
Garsed, D. W., Marshall, O. J., Corbin, V. D. A., Hsu, A., Di Stefano, L., Schröder, J., Li, J., Feng, Z.-P., Kim, B. W., Kowarsky, M., et al. (2014) · Cancer Cell · doi:10.1016/j.ccell.2014.09.010 · Cited by 194 · see citing works
Convergent somatic mutations in metabolism genes in chronic liver disease
Ng, S. W. K., Rouhani, F. J., Brunner, S. F., Brzozowska, N., Aitken, S. J., Yang, M., Abascal, F., Moore, L., Nikitopoulou, E., Chappell, L., et al. (2021) · Nature · doi:10.1038/s41586-021-03974-6 · Cited by 190 · see citing works
Self-citationEvolution of the cancer genome
Podlaha, O., Riester, M., De, S., & Michor, F. (2012) · Trends in Genetics · doi:10.1016/j.tig.2012.01.003 · Cited by 188 · see citing works
Osteosarcoma: Molecular Pathogenesis and iPSC Modeling
Lin, Y.-H., Jewell, B. E., Gingold, J., Lu, L., Zhao, R., Wang, L. L., & Lee, D.-F. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.06.004 · Cited by 150 · see citing works
Gardner, H. L., Sivaprakasam, K., Briones, N., Zismann, V., Perdigones, N., Drenner, K., Facista, S., Richholt, R., Liang, W., Aldrich, J., et al. (2019) · Communications Biology · doi:10.1038/s42003-019-0487-2 · Cited by 120 · see citing works
Cancer Genomes Evolve by Pulverizing Single Chromosomes
Meyerson, M., & Pellman, D. (2011) · Cell · doi:10.1016/j.cell.2010.12.025 · Cited by 115 · see citing works
Koirala, P., Roth, M. E., Gill, J., Chinai, J. M., Ewart, M. R., Piperdi, S., Geller, D. S., Hoang, B. H., Fatakhova, Y. V., Ghorpade, M., et al. (2016) · Scientific Reports · doi:10.1038/srep31154 · Cited by 100 · see citing works
Nones, K., Johnson, J., Newell, F., Patch, A. M., Thorne, H., Kazakoff, S. H., de Luca, X. M., Parsons, M. T., Ferguson, K., Reid, L. E., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz132 · Cited by 93 · see citing works
“Whilst these patterns of rearrangements have been reported in BC [28, 29], they have not been associated with a germline predisposition.”
Self-citationThe circular RNome of primary breast cancer
Smid, M., Wilting, S. M., Uhr, K., Rodríguez-González, F. G., de Weerd, V., Prager-Van der Smissen, W. J. C., van der Vlugt-Daane, M., van Galen, A., Nik-Zainal, S., Butler, A., et al. (2019) · Genome Research · doi:10.1101/gr.238121.118 · Cited by 105 · see citing works
Self-citationMTOR signaling orchestrates stress-induced mutagenesis, facilitating adaptive evolution in cancer
Cipponi, A., Goode, D. L., Bedo, J., McCabe, M. J., Pajic, M., Croucher, D. R., Rajal, A. G., Junankar, S. R., Saunders, D. N., Lobachevsky, P., et al. (2020) · Science · doi:10.1126/science.aau8768 · Cited by 103 · see citing works
Numerical chromosomal instability mediates susceptibility to radiation treatment
Bakhoum, S. F., Kabeche, L., Wood, M. D., Laucius, C. D., Qu, D., Laughney, A. M., Reynolds, G. E., Louie, R. J., Phillips, J., Chan, D. A., et al. (2015) · Nature Communications · doi:10.1038/ncomms6990 · Cited by 95 · see citing works
CGAS is a micronucleophagy receptor for the clearance of micronuclei
Zhao, M., Wang, F., Wu, J., Cheng, Y., Cao, Y., Wu, X., Ma, M., Tang, F., Liu, Z., Liu, H., et al. (2021) · Autophagy · doi:10.1080/15548627.2021.1899440 · Cited by 89 · see citing works
Jedrzejczak-Silicka, M. (2017) · New Insights into Cell Culture Technology · doi:10.5772/66905 · Cited by 87 · see citing works
Heterogeneity in the inter-tumor transcriptome of high risk prostate cancer
Wyatt, A. W., Mo, F., Wang, K., McConeghy, B., Brahmbhatt, S., Jong, L., Mitchell, D. M., Johnston, R. L., Haegert, A., Li, E., et al. (2014) · Genome Biology · doi:10.1186/s13059-014-0426-y · Cited by 82 · see citing works
Genome Sequencing during a Patient’s Journey through Cancer
Nangalia, J., & Campbell, P. J. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1910138 · Cited by 66 · see citing works
Self-citationAutism Spectrum Disorder Genetics: Diverse Genes with Diverse Clinical Outcomes
Talkowski, M. E., Minikel, E. V., & Gusella, J. F. (2014) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000002 · Cited by 72 · see citing works
Induced dicentric chromosome formation promotes genomic rearrangements and tumorigenesis
Gascoigne, K. E., & Cheeseman, I. M. (2013) · Chromosome Research · doi:10.1007/s10577-013-9368-6 · Cited by 65 · see citing works
Detection of circulating tumor DNA in patients with osteosarcoma
Barris, D. M., Weiner, S. B., Dubin, R. A., Fremed, M., Zhang, X., Piperdi, S., Zhang, W., Maqbool, S., Gill, J., Roth, M., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.24268 · Cited by 63 · see citing works
Ratnaparkhe, M., Hlevnjak, M., Kolb, T., Jauch, A., Maass, K. K., Devens, F., Rode, A., Hovestadt, V, Korshunov, A., Pastorczak, A., et al. (2017) · Leukemia · doi:10.1038/leu.2017.55 · Cited by 63 · see citing works
Głodzik, D., Purdie, C., Rye, I. H., Simpson, P. T., Staaf, J., Span, P. N., Russnes, H. G., & Nik-Zainal, S. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy404 · Cited by 45 · see citing works
Self-citationPoly‐gene fusion transcripts and chromothripsis in prostate cancer
Wu, C., Wyatt, A. W., McPherson, A., Lin, D., McConeghy, B. J., Mo, F., Shukin, R., Lapuk, A. V., M. Jones, S. J., Zhao, Y., et al. (2012) · Genes, Chromosomes and Cancer · doi:10.1002/gcc.21999 · Cited by 51 · see citing works
Copy number alterations unmasked as enhancer hijackers
Beroukhim, R., Zhang, X., & Meyerson, M. (2017) · Nature Genetics · doi:10.1038/ng.3754 · Cited by 46 · see citing works
Patient Derived Xenografts for Genome-Driven Therapy of Osteosarcoma
Landuzzi, L., Manara, M. C., Lollini, P.-L., & Scotlandi, K. (2021) · Cells · doi:10.3390/cells10020416 · Cited by 39 · see citing works
Genome-wide methylated CpG island profiles of melanoma cells reveal a melanoma coregulation network
Li, J.-L., Mazar, J., Zhong, C., Faulkner, G. J., Govindarajan, S. S., Zhang, Z., Dinger, M. E., Meredith, G., Adams, C., Zhang, S., et al. (2013) · Scientific Reports · doi:10.1038/srep02962 · Cited by 21 · see citing works
Mills, L. J., Spector, L. G., Largaespada, D. A., & Williams, L. A. (2021) · Biology of Sex Differences · doi:10.1186/s13293-020-00347-y · Cited by 17 · see citing works
Rajan, S., Zaccaria, S., Cannon, M. V., Cam, M., Gross, A. C., Raphael, B. J., & Roberts, R. D. (2021) · doi:10.1101/2021.08.30.458268 · Cited by 33 · see citing works
- Authors
- Stephens, P. J., Greenman, C. D., Fu, B., Yang, F., Bignell, G. R., Mudie, L. J., Pleasance, E. D., Lau, K. W., Beare, D., Stebbings, L. A., McLaren, S., Lin, M.-L., McBride, D. J., Varela, I., Nik-Zainal, S., Leroy, C., Jia, M., Menzies, A., Butler, A. P., Teague, J. W., Quail, M. A., Burton, J., Swerdlow, H., Carter, N. P., Morsberger, L. A., Iacobuzio-Donahue, C., Follows, G. A., Green, A. R., Flanagan, A. M., Stratton, M. R., Futreal, P. A., & Campbell, P. J.
- Affiliations
- Wellcome Sanger Institute (GB)
- Johns Hopkins University (US)
- Addenbrooke's Hospital (GB)
- University of Cambridge (GB)
- Royal National Orthopaedic Hospital (GB)
- Corresponding author
- Campbell, Peter J.
- ORCID
- Greenman, Chris D.
- Fu, Beiyuan
- Yang, Fengtang
- Pleasance, Erin D.
- Lau, King Wai
- McLaren, Stuart
- Lin, Meng-Lay
- McBride, David J.
- Varela, Ignacio
- Jia, Mingming
- Menzies, Andrew
- Teague, Jon W.
- Quail, Michael A.
- Swerdlow, Harold
- Follows, George A.
- Green, Anthony R.
- Flanagan, Adrienne M.
- Stratton, Michael R.
- Futreal, P. Andrew
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 144
- Issue
- 1
- Pages
- 27-40
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3065307
- OpenAlex
- W2109948920
- Cited by
- 2,414
- References
- 36
- Citations by year
- 2026: 91 · 2025: 121 · 2024: 142 · 2023: 122 · 2022: 123 · 2021: 185 · 2020: 162 · 2019: 142 · 2018: 164 · 2017: 147 · 2016: 181 · 2015: 186 · 2014: 197 · 2013: 191 · 2012: 169
- FWCI
- 69.77
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Funders
- Wellcome Trust (077012/Z/05/Z, 088340, 093867, WT088340MA)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
- Keywords
- chromothripsis, chromosomal rearrangements, genomic instability, tumor origin, bone cancer, somatic mutations, tumor evolution
- MeSH terms
- Bone Neoplasms, Chromosome Aberrations, Female, Humans, Middle Aged, Neoplasms, Gene Rearrangement, Leukemia, Lymphocytic, Chronic, B-Cell, Chromosome Painting, Cell Line, Tumor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
