Cited by 709Cancer Genomics and DiagnosticsGenomic variations and chromosomal abnormalitiesChromatin Remodeling and Cancer

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Signatures of mutation and selection in the cancer genome

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Bignell, Graham R., Greenman, Chris D., Davies, Helen, Butler, Adam P., Edkins, Sarah, Andrews, Jenny M., Buck, Gemma, Chen, Lina, Beare, David, Latimer, Calli, Widaa, Sara, Hinton, Jonathon, Fahey, Ciara, Fu, Beiyuan, Swamy, Sajani, Dalgliesh, Gillian L., Teh, Bin T., Deloukas, Panos, Yang, Fengtang, Campbell, Peter J., Futreal, P. Andrew, Stratton, Michael R.·2010·Nature

DOI 10.1038/nature08768PMC PMC3145113

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Abstract

The cancer genome is moulded by the dual processes of somatic mutation and selection. Homozygous deletions in cancer genomes occur over recessive cancer genes, where they can confer selective growth advantage, and over fragile sites, where they are thought to reflect an increased local rate of DNA breakage. However, most homozygous deletions in cancer genomes are unexplained. Here we identified 2,428 somatic homozygous deletions in 746 cancer cell lines. These overlie 11% of protein-coding genes that, therefore, are not mandatory for survival of human cells. We derived structural signatures that distinguish between homozygous deletions over recessive cancer genes and fragile sites. Application to clusters of unexplained homozygous deletions suggests that many are in regions of inherent fragility, whereas a small subset overlies recessive cancer genes. The results illustrate how structural signatures can be used to distinguish between the influences of mutation and selection in cancer genomes. The extensive copy number, genotyping, sequence and expression data available for this large series of publicly available cancer cell lines renders them informative reagents for future studies of cancer biology and drug discovery. Two Articles in this issue add major data sets to the growing picture of the cancer genome. Bignell et al. analysed a large number of homozygous gene deletions in a collection of 746 publicly available cancer cell lines. Combined with information about hemizygous deletions of the same genes, the data suggest that many deletions found in cancer reflect the position of a gene at a fragile site in the genome, rather than as a recessive cancer gene whose loss confers a selective growth advantage. Beroukhim et al. present the largest data set to date on somatic copy-number variations across more than 3,000 specimens of human primary cancers. Many alterations are shared between multiple tumour types. Functional experiments demonstrate an oncogenic role for the apoptosis genes MCL1 and BCL2L1 that are associated with amplifications found in many cancers. Homozygous gene deletions in cancer cells occur over recessive cancer genes (where they can confer selective growth advantage) or over genes at fragile sites of the genome (where they are thought to reflect increased DNA breakage). Here, a large number of homozygous deletions in a collection of cancer cell lines are identified and analysed to derive structural signatures for the two different types of deletion. More deletions are found in inherently fragile regions, and fewer overlying recessive genes.

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1 retracted

A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function
Melo, S. A., Ropero, S., Moutinho, C., Aaltonen, L. A., Yamamoto, H., Calin, G. A., Rossi, S., Fernández, A. F., Carneiro, F., Oliveíra, C., et al. (2009) · Nature Genetics · doi:10.1038/ng.317 · Cited by 375
Retracted
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482
PTEN , a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer
Li, J., Yen, C., Liaw, D., Podsypanina, K., Bose, S., Wang, S. I., Puc, J., Miliaresis, C., Rodgers, L., McCombie, R., et al. (1997) · Science · doi:10.1126/science.275.5308.1943 · Cited by 4,785
The cancer genome
Stratton, M. R., Campbell, P. J., & Futreal, P. A. (2009) · Nature · doi:10.1038/nature07943 · Cited by 3,625
Self-citation
The Consensus Coding Sequences of Human Breast and Colorectal Cancers
Sjöblom, T., Jones, S., Wood, L. D., Parsons, D. W., Lin, J., Barber, T. D., Mandelker, D. L., Leary, R. J., Ptak, J., Silliman, N., et al. (2006) · Science · doi:10.1126/science.1133427 · Cited by 3,161
Somatic mutations affect key pathways in lung adenocarcinoma
Ding, L., Getz, G., Wheeler, D. A., Mardis, E. R., McLellan, M. D., Cibulskis, K., Sougnez, C., Greulich, H., Muzny, D. M., Morgan, M. B., et al. (2008) · Nature · doi:10.1038/nature07423 · Cited by 2,681
Inactivation of the Type II TGF-β Receptor in Colon Cancer Cells with Microsatellite Instability
Markowitz, S. D., Wang, J., Myeroff, L. L., Parsons, R. E., Sun, L., Lutterbaugh, J., Fan, R. S., Zborowska, E., Kinzler, K. W., Vogelstein, B., et al. (1995) · Science · doi:10.1126/science.7761852 · Cited by 2,267
Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions
Gorgoulis, V. G., Vassiliou, L.-V. F., Karakaidos, P., Zacharatos, P., Kotsinas, A., Liloglou, T., Venere, M., DiTullio, R. A., Kastrinakis, N. G., Levy, B., et al. (2005) · Nature · doi:10.1038/nature03485 · Cited by 2,009
Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer
Versteege, I., Sévenet, N., Lange, J., Rousseau-Merck, M.-F., Ambros, P. F., Handgretinger, R., Aurias, A., & Delattre, O. (1998) · Nature · doi:10.1038/28212 · Cited by 1,552
The cytoplasmic domain of the cell adhesion molecule uvomorulin associates with three independent proteins structurally related in different species.
Ozawa, M., Baribault, H., & Kemler, R. (1989) · The EMBO Journal · doi:10.1002/j.1460-2075.1989.tb03563.x · Cited by 1,396

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Miron, K., Golan‐Lev, T., Dvir-Szternfeld, R., Ben‐David, E., & Kerem, B. (2015) · Nature Communications · doi:10.1038/ncomms8094 · Cited by 88
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Teh, M., Gemenetzidis, E., Patel, D., Tariq, R., Nadir, A., Bahta, A. W., Waseem, A., & Hutchison, I. L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034329 · Cited by 83
WWOX, the common fragile site FRA16D gene product, regulates ATM activation and the DNA damage response
Abu-Odeh, M., Salah, Z., Herbel, C., Hofmann, T. G., & Aqeilan, R. I. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1409252111 · Cited by 86
Expression and clinical significances of Beclin1, LC3 and mTOR in colorectal cancer.
Wu, S., Sun, C., Tian, D., Li, Y., Gao, X., He, S., & Li, T. (2015) · Europe PMC (PubMed Central) · Cited by 83
Genomic signature of Fanconi anaemia DNA repair pathway deficiency in cancer
Webster, A., Sanders, M. A., Patel, K., Dietrich, R., Noonan, R. J., Lach, F. P., White, R. R., Goldfarb, A. M., Hadi, K., Edwards, M. M., et al. (2022) · Nature · doi:10.1038/s41586-022-05253-4 · Cited by 96
Self-citation
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Greaves, M. F. (2012) · Evolutionary Applications · doi:10.1111/eva.12017 · Cited by 85
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Ozeri-Galai, E., Bester, A. C., & Kerem, B. (2012) · Trends in Genetics · doi:10.1016/j.tig.2012.02.006 · Cited by 84
Phylomedicine: an evolutionary telescope to explore and diagnose the universe of disease mutations
Kumar, S., Dudley, J. T., Filipski, A., & Liu, L. (2011) · Trends in Genetics · doi:10.1016/j.tig.2011.06.004 · Cited by 81
WWOX-related encephalopathies: delineation of the phenotypical spectrum and emerging genotype-phenotype correlation
Mignot, C., Lambert, L., Pasquier, L., Bienvenu, T., Delahaye‐Duriez, A., Keren, B., Lefranc, J., Saunier, A., Allou, L., Roth, V., et al. (2014) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2014-102748 · Cited by 82
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Özer, Ö., & Hickson, I. D. (2018) · Open Biology · doi:10.1098/rsob.180018 · Cited by 83
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Dereli‐Öz, A., Versini, G., & Halazonetis, T. D. (2011) · Molecular Oncology · doi:10.1016/j.molonc.2011.05.002 · Cited by 82
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White, K. A., Ruiz, D. G., Szpiech, Z. A., Strauli, N. B., Hernandez, R. D., Jacobson, M. P., & Barber, D. L. (2017) · Science Signaling · doi:10.1126/scisignal.aam9931 · Cited by 79
3D genome organization contributes to genome instability at fragile sites
Sarni, D., Sasaki, T., Sinai, M. I., Miron, K., Rivera‐Mulia, J. C., Magnuson, B., Ljungman, M. E., Gilbert, D. M., & Kerem, B. (2020) · Nature Communications · doi:10.1038/s41467-020-17448-2 · Cited by 86
RPA Inhibition Increases Replication Stress and Suppresses Tumor Growth
Glanzer, J. G., Liu, S., Wang, L., Mosel, A., Peng, A., & Oakley, G. G. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-0306 · Cited by 79
Structural mutations in cancer: mechanistic and functional insights
Inaki, K., & Liu, E. T. (2012) · Trends in Genetics · doi:10.1016/j.tig.2012.07.002 · Cited by 75
Transcription factor Dlx2 protects from TGFβ‐induced cell‐cycle arrest and apoptosis
Yilmaz, M., Maaß, D., Tiwari, N., Waldmeier, L., Schmidt, P., Lehembre, F., & Christofori, G. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.319 · Cited by 76
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Czyż, M. (2019) · Cells · doi:10.3390/cells8060540 · Cited by 74
Characterization of potential driver mutations involved in human breast cancer by computational approaches
Rajendran, B. K., & Deng, C.-X. (2017) · Oncotarget · doi:10.18632/oncotarget.17225 · Cited by 73
Protein Domain-Level Landscape of Cancer-Type-Specific Somatic Mutations
Yang, F., Petsalaki, E., Rolland, T., HILL, D. E., Vidal, M., & Roth, F. P. (2015) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1004147 · Cited by 71
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Borrell, B. (2010) · Nature · doi:10.1038/463858a · Cited by 73
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Yao, Y., Gu, X., Xu, X., Ge, S., & Jia, R. (2022) · Cancer Letters · doi:10.1016/j.canlet.2022.215870 · Cited by 72
Network biomarkers reveal dysfunctional gene regulations during disease progression
Zeng, T., Sun, S., Wang, Y., Zhu, H., & Chen, L. (2013) · FEBS Journal · doi:10.1111/febs.12536 · Cited by 72
Self-citation
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Zhao, Q., Kirkness, E. F., Caballero, O. L., Galante, P. A. F., Parmigiani, R. B., Edsall, L., Kuan, S., Ye, Z., Levy, S., de Vasconcelos, A. T. R., et al. (2010) · Genome biology · doi:10.1186/gb-2010-11-11-r114 · Cited by 61
Large chromosome deletions, duplications, and gene conversion events accumulate with age in normal human colon crypts
Hsieh, J. C. F., Berg, D. V. D., Kang, H., Hsieh, C., & Lieber, M. R. (2013) · Aging Cell · doi:10.1111/acel.12053 · Cited by 71
Focal chromosomal copy number aberrations in cancer—Needles in a genome haystack
Krijgsman, O., Carvalho, B. G., Meijer, G. A., Steenbergen, R. D. M., & Ylstra, B. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2014.08.001 · Cited by 73
Targeting EGFR in non-small-cell lung cancer: Lessons, experiences, strategies
Stella, G. M., Luisetti, M., Inghilleri, S., Cemmi, F., Scabini, R., Zorzetto, M., & Pozzi, E. (2011) · Respiratory Medicine · doi:10.1016/j.rmed.2011.10.015 · Cited by 73
Gain of MYC underlies recurrent trisomy of the MYC chromosome in acute promyelocytic leukemia
Jones, L. C., Wei, G., Ševčı́ková, S., Phan, V. T., Jain, S., Shieh, A., Wong, J. C. Y., Li, M., Dubansky, J., Maunakea, M. L., et al. (2010) · The Journal of Experimental Medicine · doi:10.1084/jem.20091071 · Cited by 71
A Single-Nucleotide Substitution Mutator Phenotype Revealed by Exome Sequencing of Human Colon Adenomas
Nikolaev, S. I., Sotiriou, S. K., Pateras, I. S., Santoni, F. A., Sougioultzis, S., Edgren, H., Almusa, H., Robyr, D., Guipponi, M., Saarela, J., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-3869 · Cited by 70
DNA replication stress: oncogenes in the spotlight
Primo, L. M. F., & Teixeira, L. K. (2019) · Genetics and Molecular Biology · doi:10.1590/1678-4685gmb-2019-0138 · Cited by 96
Targeting RB1 Loss in Cancers
Linn, P., Kohno, S., Sheng, J., Kulathunga, N., Yu, H., Zhang, Z., Voon, D. C., Watanabe, Y., & Takahashi, C. (2021) · Cancers · doi:10.3390/cancers13153737 · Cited by 70
Mechanism of Replicative DNA Polymerase Delta Pausing and a Potential Role for DNA Polymerase Kappa in Common Fragile Site Replication
Walsh, E. M., Wang, X., Lee, M. Y., & Eckert, K. A. (2012) · Journal of Molecular Biology · doi:10.1016/j.jmb.2012.11.016 · Cited by 68
Map2k4 Functions as a Tumor Suppressor in Lung Adenocarcinoma and Inhibits Tumor Cell Invasion by Decreasing Peroxisome Proliferator-Activated Receptor γ2 Expression
Ahn, Y., Yang, Y., Gibbons, D. L., Creighton, C. J., Yang, F., Wistuba, I. I., Lin, W., Thilaganathan, N., Alvarez, C. A., Roybal, J. D., et al. (2011) · Molecular and Cellular Biology · doi:10.1128/mcb.05562-11 · Cited by 68
Self-citation
Molecular Profiling of Cancer—The Future of Personalized Cancer Medicine: A Primer on Cancer Biology and the Tools Necessary to Bring Molecular Testing to the Clinic
Stricker, T. P., Catenacci, D. V. T., & Seiwert, T. Y. (2011) · Seminars in Oncology · doi:10.1053/j.seminoncol.2011.01.013 · Cited by 68

Authors: Bignell, G. R., Greenman, C. D., Davies, H., Butler, A. P., Edkins, S., Andrews, J. M., Buck, G., Chen, L., Beare, D., Latimer, C., Widaa, S., Hinton, J., Fahey, C., Fu, B., Swamy, S., Dalgliesh, G. L., Teh, B. T., Deloukas, P., Yang, F., Campbell, P. J., Futreal, P. A., & Stratton, M. R.
Affiliations: Wellcome Sanger Institute (GB)
Van Andel Institute (US)
Institute of Cancer Research (GB)
Corresponding author: Futreal, P. Andrew
Stratton, Michael R.
ORCID: Greenman, Chris D.
Davies, Helen
Edkins, Sarah
Buck, Gemma
Chen, Lina
Latimer, Calli
Widaa, Sara
Fu, Beiyuan
Dalgliesh, Gillian L.
Teh, Bin T.
Deloukas, Panos
Yang, Fengtang
Campbell, Peter J.
Futreal, P. Andrew
Stratton, Michael R.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2010-02
Volume: 463
Issue: 7283
Pages: 893-898
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature08768
PMC: PMC3145113
OpenAlex: W2071734901
Cited by: 707
References: 41
Citations by year: 2026: 7 · 2025: 24 · 2024: 21 · 2023: 29 · 2022: 25 · 2021: 32 · 2020: 40 · 2019: 30 · 2018: 44 · 2017: 44 · 2016: 47 · 2015: 48 · 2014: 61 · 2013: 71 · 2012: 76
FWCI: 25.43
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/3.0/ (tdm)
Locations: Nature (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
UEA Digital Repository (University of East Anglia) (submittedVersion)
Funders: Wellcome Trust (077012/Z/05/Z, 088340, 093867)
National Cancer Institute (P01CA155258)
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 › Molecular Biology › Chromatin Remodeling and Cancer
Keywords: fragile sites, copy number variation, cancer cell lines, structural signatures, DNA breakage, Mcl-1, Bcl-xL, gene amplification, tumor suppressor
MeSH terms: Chromosomes, Human, DNA Mutational Analysis, Genes, Recessive, Homozygote, Humans, Models, Genetic, Neoplasms, Selection, Genetic, Reproducibility of Results, Genome, Human, Gene Deletion, Gene Dosage, Physical Chromosome Mapping, Oligonucleotide Array Sequence Analysis, Chromosome Fragile Sites, Cell Line, Tumor, Genes, Neoplasm, DNA Copy Number Variations

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