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A comprehensive catalogue of somatic mutations from a human cancer genome
Open accessAbstract
All cancers carry somatic mutations. A subset of these somatic alterations, termed driver mutations, confer selective growth advantage and are implicated in cancer development, whereas the remainder are passengers. Here we have sequenced the genomes of a malignant melanoma and a lymphoblastoid cell line from the same person, providing the first comprehensive catalogue of somatic mutations from an individual cancer. The catalogue provides remarkable insights into the forces that have shaped this cancer genome. The dominant mutational signature reflects DNA damage due to ultraviolet light exposure, a known risk factor for malignant melanoma, whereas the uneven distribution of mutations across the genome, with a lower prevalence in gene footprints, indicates that DNA repair has been preferentially deployed towards transcribed regions. The results illustrate the power of a cancer genome sequence to reveal traces of the DNA damage, repair, mutation and selection processes that were operative years before the cancer became symptomatic. The two cancer genome sequences presented in this issue demonstrate how next-generation sequencing technologies can inform us about mutational processes, repair pathways and gene networks associated with cancer development. First, the genome of a cell line derived from a bone marrow metastasis in a patient who had small-cell lung cancer. This cancer is typical of the type induced by smoking, and the sequence contains mutation signatures characteristic of some of the more than 60 carcinogens present in tobacco smoke. The second paper compares the whole genome sequence of a melanoma cell line to a lymphoblastoid cell line from the same individual. This, the first complete mutational analysis of a solid tumour, reveals a dominant mutational signature reflecting DNA damage due to exposure to ultraviolet light. Here, the genomes of a malignant melanoma and a lymphoblastoid cell line from the same person are sequenced, providing the first comprehensive catalogue of somatic mutations from an individual cancer. The data provide insight into the causes of tumour formation and the development of the cancer genome, with the dominant mutational signature reflecting DNA damage due to ultraviolet light exposure.
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“Melanoma somatic mutations consist almost entirely of C → T transitions, 28% of which are TCC → T mutations (19,31).”
From Evidence for recent, population-specific evolution of the human mutation rate (2015) · cites this paper as [31]
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Cites
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607
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 11,029
Velvet: Algorithms for de novo short read assembly using de Bruijn graphsPreprint
Zerbino, D. R., & Birney, E. (2008) · Genome Research · doi:10.1101/gr.074492.107 · Cited by 9,575
Comprehensive genomic characterization defines human glioblastoma genes and core pathways
The Cancer Genome Atlas Research Network (2008) · Nature · doi:10.1038/nature07385 · Cited by 7,735
Genome sequencing in microfabricated high-density picolitre reactors
Margulies, M., Egholm, M., Altman, W. E., Attiya, S., Bader, J. S., Bemben, L. A., Berka, J., Braverman, M. S., Chen, Y.-J., Chen, Z., et al. (2005) · Nature · doi:10.1038/nature03959 · Cited by 7,693
An Integrated Genomic Analysis of Human Glioblastoma Multiforme
Parsons, D. W., Jones, S., Zhang, X., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Siu, I.-M., Gallia, G. L., et al. (2008) · Science · doi:10.1126/science.1164382 · Cited by 5,857
Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
Jones, S., Zhang, X., Parsons, D. W., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., et al. (2008) · Science · doi:10.1126/science.1164368 · Cited by 3,969
Self-citationAccurate whole human genome sequencing using reversible terminator chemistry
Bentley, D. R., Balasubramanian, S., Swerdlow, H. P., Smith, G. P., Milton, J., Brown, C. G., Hall, K. P., Evers, D. J., Barnes, C. L., Bignell, H. R., et al. (2008) · Nature · doi:10.1038/nature07517 · Cited by 3,684
Self-citationStratton, M. R., Campbell, P. J., & Futreal, P. A. (2009) · Nature · doi:10.1038/nature07943 · Cited by 3,625
Self-citationA census of human cancer genes
Futreal, P. A., Coin, L., Marshall, M., Down, T., Hubbard, T., Wooster, R., Rahman, N., & Stratton, M. R. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1299 · Cited by 3,184
Self-citationPatterns of somatic mutation in human cancer genomes
Greenman, C. D., Stephens, P., Smith, R., Dalgliesh, G. L., Hunter, C., Bignell, G. R., Davies, H. R., Teague, J. W., Butler, A. P., Stevens, C., et al. (2007) · Nature · doi:10.1038/nature05610 · Cited by 3,062
Self-citationThe Genomic Landscapes of Human Breast and Colorectal Cancers
Wood, L. D., Parsons, D. W., Jones, S., Lin, J., Sjöblom, T., Leary, R. J., Shen, D., Boca, S. M., Barber, T., Ptak, J., et al. (2007) · Science · doi:10.1126/science.1145720 · Cited by 2,833
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
Mapping 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
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
Ye, K., Schulz, M. H., Long, Q., Apweiler, R., & Ning, Z. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp394 · Cited by 2,017
Self-citationThe epidemiology of UV induced skin cancer
Armstrong, B. K., & Kricker, A. (2001) · Journal of Photochemistry and Photobiology B: Biology · doi:10.1016/s1011-1344(01)00198-1 · Cited by 1,811
DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome
Ley, T. J., Mardis, E. R., Ding, L., Fulton, B., McLellan, M. D., Chen, K., Dooling, D. J., Dunford-Shore, B. H., McGrath, S. D., Hickenbotham, M. T., et al. (2008) · Nature · doi:10.1038/nature07485 · Cited by 1,434
Transcription-coupled DNA repair: two decades of progress and surprises
Hanawalt, P. C., & Spivak, G. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2549 · Cited by 1,081
Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG
Liang, C., Feng, P., Ku, B., Dotan, I., Canaani, D., Oh, B.-H., & Jung, J. U. (2006) · Nature Cell Biology · doi:10.1038/ncb1426 · Cited by 919
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 827
Self-citationMutations induced by ultraviolet light
Pfeifer, G. P., You, Y., & Nia, A. B. (2005) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2004.06.057 · Cited by 798
Epidemiology of Melanoma and Nonmelanoma Skin Cancer—The Role of Sunlight
Leiter, U., & Garbe, C. (2009) · Advances in experimental medicine and biology · doi:10.1007/978-0-387-77574-6_8 · Cited by 733
Robertson, A. B., Klungland, A., Rognes, T., & Leiros, I. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-8736-z · Cited by 685
Mitochondrial DNA mutations in human cancer
Chatterjee, A., Mambo, E., & Sidransky, D. (2006) · Oncogene · doi:10.1038/sj.onc.1209604 · Cited by 586
Fousteri, M., & Mullenders, L. H. (2008) · Cell Research · doi:10.1038/cr.2008.6 · Cited by 487
Kawanishi, S., Hiraku, Y., & Oikawa, S. (2001) · Mutation Research/Reviews in Mutation Research · doi:10.1016/s1383-5742(00)00059-4 · Cited by 444
DNA Repair in Mammalian Cells: Nucleotide excision repair: variations on versatility
Nouspikel, T. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-8737-y · Cited by 330
TP53 mutations in human skin cancers
Giglia‐Mari, G., & Sarasin, A. R. (2003) · Human Mutation · doi:10.1002/humu.10179 · Cited by 298
Eukaryotic nucleotide excision repair: from understanding mechanisms to influencing biology
Shuck, S. C., Short, E. A., & Turchi, J. J. (2008) · Cell Research · doi:10.1038/cr.2008.2 · Cited by 289
Oettgen, P., Finger, E., Sun, Z., Akbarali, Y., Thamrongsak, U., Boltax, J., Grall, F., Dube, A., Weiss, A., Brown, L., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.2.1216 · Cited by 268
Mutational spectra of human cancer
Pfeifer, G. P., & Nia, A. B. (2009) · Human Genetics · doi:10.1007/s00439-009-0657-2 · Cited by 180
Statistical Analysis of Pathogenicity of Somatic Mutations in Cancer
Greenman, C., Wooster, R., Futreal, P. A., Stratton, M. R., & Easton, D. F. (2006) · Genetics · doi:10.1534/genetics.105.044677 · Cited by 163
Self-citationAnalysis of the matrix metalloproteinase family reveals that MMP8 is often mutated in melanoma
Palavalli, L. H., Prickett, T. D., Wunderlich, J. R., Wei, X., Burrell, A. S., Porter-Gill, P. A., Davis, S. R., Wang, C., Cronin, J. C., Agrawal, N., et al. (2009) · Nature Genetics · doi:10.1038/ng.340 · Cited by 162
Futreal, P. A., Kasprzyk, A., Birney, E., Mullikin, J. C., Wooster, R., & Stratton, M. R. (2001) · Nature · doi:10.1038/35057046 · Cited by 152
Self-citationDaya-Grosjean, L., & Sarasin, A. (2005) · Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis · doi:10.1016/j.mrfmmm.2004.11.013 · Cited by 142
Human Ccr4‐Not complex is a ligand‐dependent repressor of nuclear receptor‐mediated transcription
Winkler, G. S., Mulder, K. W., Bardwell, V. J., Kalkhoven, E., & Timmers, H. T. M. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601194 · Cited by 98
Sood, A. K., Saxena, R., Groth, J., Desouki, M. M., Cheewakriangkrai, C., Rodabaugh, K. J., Kasyapa, C. S., & Geradts, J. (2007) · Human Pathology · doi:10.1016/j.humpath.2007.03.010 · Cited by 65
Scaglioni, P. P., & Pandolfi, P. P. (2007) · Springer eBooks · doi:10.1007/978-3-540-34594-7_6 · Cited by 47
Ghadersohi, A., Odunsi, K. O., Zhang, S., Azrak, R. G., Bundy, B. N., Manjili, M. H., & Li, F. (2008) · International Journal of Cancer · doi:10.1002/ijc.23667 · Cited by 29
Cytogenetic homogeneity in eight independent sites in a case of malignant melanoma
Morse, H. G., & Moore, G. E. (1993) · Cancer Genetics and Cytogenetics · doi:10.1016/0165-4608(93)90083-x · Cited by 23
Teitz, T., Penner, M., Eli, D., Stark, M., Bakhanashvili, M., Naiman, T., & Canaani, D. (1990) · Gene · doi:10.1016/0378-1119(90)90316-j · Cited by 23
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A framework for variation discovery and genotyping using next-generation DNA sequencing data
DePristo, M. A., Banks, E., Poplin, R. E., Garimella, K. V., Maguire, J., Hartl, C., Philippakis, A., del Angel, G., Rivas, M. A., Hanna, M., et al. (2011) · Nature Genetics · doi:10.1038/ng.806 · Cited by 11,457
Li, H. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr509 · Cited by 6,454
Mutational heterogeneity in cancer and the search for new cancer-associated genes
Lawrence, M. S., Stojanov, P., Polak, P., Kryukov, G. V., Cibulskis, K., Sivachenko, A., Carter, S. L., Stewart, C., Mermel, C. H., Roberts, S. A., et al. (2013) · Nature · doi:10.1038/nature12213 · Cited by 5,461
Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples
Cibulskis, K., Lawrence, M. S., Carter, S. L., Sivachenko, A., Jaffe, D. B., Sougnez, C. L., Gabriel, S., Meyerson, M. M., Lander, E. S., & Getz, G. A. (2013) · Nature Biotechnology · doi:10.1038/nbt.2514 · Cited by 4,926
The DNA Damage Response: Making It Safe to Play with Knives
Ciccia, A., & Elledge, S. J. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.019 · Cited by 4,368
Metadata
- Authors
- 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., Ye, K., Alipaz, J., Bauer, M. J., Beare, D., Butler, A., Carter, R. J., Chen, L., Cox, A. J., Edkins, S., Kokko-Gonzales, P. I., Gormley, N. A., Grocock, R. J., Haudenschild, C. D., Hims, M. M., James, T., Jia, M., Kingsbury, Z., Leroy, C., Marshall, J., Menzies, A., Mudie, L. J., Ning, Z., Royce, T., Schulz-Trieglaff, O. B., Spiridou, A., Stebbings, L. A., Szajkowski, L., Teague, J., Williamson, D., Chin, L., Ross, M. T., Campbell, P. J., Bentley, D. R., Futreal, P. A., & Stratton, M. R.
- Affiliations
- Wellcome Sanger Institute (GB)
- Illumina (United Kingdom) (GB)
- Leiden University Medical Center (NL)
- Illumina (United States) (US)
- Dana-Farber Cancer Institute (US)
- Institute of Cancer Research (GB)
- Corresponding author
- Futreal, P. Andrew
- Stratton, Michael R.
- ORCID
- Pleasance, Erin D.
- McBride, David J.
- Humphray, Sean J.
- Greenman, Chris D.
- Varela, Ignacio
- Lin, Meng-Lay
- Ye, Kai
- Bauer, Markus J.
- Chen, Lina
- Edkins, Sarah
- James, Terena
- Jia, Mingming
- Marshall, John
- Menzies, Andrew
- Ning, Zemin
- Spiridou, Anastassia
- Teague, Jon
- Ross, Mark T.
- Campbell, Peter J.
- Futreal, P. Andrew
- Stratton, Michael R.
- Venue
- Nature
- Published
- 2009-12-16
- Volume
- 463
- Issue
- 7278
- Pages
- 191-196
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3145108
- OpenAlex
- W2150677022
- Cited by
- 1,696
- References
- 43
- Citations by year
- 2026: 23 · 2025: 47 · 2024: 43 · 2023: 49 · 2022: 50 · 2021: 83 · 2020: 76 · 2019: 87 · 2018: 69 · 2017: 94 · 2016: 121 · 2015: 116 · 2014: 144 · 2013: 166 · 2012: 189
- FWCI
- 58.62
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Funders
- Wellcome Trust (077012/Z/05/Z, 077012, 088340, 093867)
- Kay Kendall Leukaemia Fund
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- somatic mutations, mutational signatures, melanoma, lymphoblastoid cell lines, DNA repair, small cell lung cancer, tobacco smoke carcinogens, driver mutations, passenger mutations, cancer genome evolution
- MeSH terms
- Adult, DNA Damage, DNA Mutational Analysis, DNA Repair, Humans, Male, Melanoma, Mutation, Neoplasms, Ultraviolet Rays, Genome, Human, Mutagenesis, Insertional, Sequence Deletion, Gene Dosage, Loss of Heterozygosity, Polymorphism, Single Nucleotide, MicroRNAs, Cell Line, Tumor, Genes, Neoplasm, Precision Medicine
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