Universal Patterns of Selection in Cancer and Somatic Tissues
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Abstract
Cancer develops as a result of somatic mutation and clonal selection, but quantitative measures of selection in cancer evolution are lacking. We adapted methods from molecular evolution and applied them to 7,664 tumors across 29 cancer types. Unlike species evolution, positive selection outweighs negative selection during cancer development. On average, <1 coding base substitution/tumor is lost through negative selection, with purifying selection almost absent outside homozygous loss of essential genes. This allows exome-wide enumeration of all driver coding mutations, including outside known cancer genes. On average, tumors carry ∼4 coding substitutions under positive selection, ranging from <1/tumor in thyroid and testicular cancers to >10/tumor in endometrial and colorectal cancers. Half of driver substitutions occur in yet-to-be-discovered cancer genes. With increasing mutation burden, numbers of driver mutations increase, but not linearly. We systematically catalog cancer genes and show that genes vary extensively in what proportion of mutations are drivers versus passengers.
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The dN/dS ratio test confirmed that somatic variants in Alzheimer's disease brains experienced stronger positive selection than somatic variants in control brains, with greater than a 350% increase in positively selected cells.
“Direct examination of the signal of positive selection on these variants using the dN/dS ratio test36 confirmed that somatic variants in AD brains experienced stronger positive selection than somatic variants in control brains (Figure 2H-I), with greater than a 350% increase in positively selected cells (Figure 2J).”
From Somatic cancer variants enriched in Alzheimer’s disease microglia-like cells drive inflammatory and proliferative states (2026) · cites this paper as [36]
The 285 developmental-disorder-associated genes significantly overlap 369 previously described cancer driver genes, with 70 genes overlapping (p = 1.7 × 10-49).
“We observed a significant overlap between the 285 DNM-enriched DD-associated genes and a set of 369 previously described cancer driver genes19 (overlap of 70 genes; p = 1.7 × 10-49, logistic regression correcting for shet), as observed previously20,21, as well as a significant enrichment of nonsynonymous DNMs in both overlapping and non-overlapping cancer genes (Supplementary Table 9).”
From Evidence for 28 genetic disorders discovered by combining healthcare and research data (2020) · cites this paper as [19]
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Cites
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 · see citing works
A global reference for human genetic variation
The 1000 Genomes Project Consortium, authors, C., Auton, A., Abecasis, G. R., Steering committee, Altshuler, D. M., Durbin, R. M., Abecasis, G. R., Bentley, D. R., Chakravarti, A., et al. (2015) · Nature · doi:10.1038/nature15393 · Cited by 18,247 · see citing works
PAML 4: Phylogenetic Analysis by Maximum Likelihood
Yang, Z. (2007) · Molecular Biology and Evolution · doi:10.1093/molbev/msm088 · Cited by 13,879 · see citing works
Signatures of mutational processes in human cancer
Initiative, A. P. C. G., Alexandrov, L. B., ICGC Breast Cancer Consortium, ICGC MMML-Seq Consortium, PedBrain, I., Nik-Zainal, S., Wedge, D. C., Aparicio, S. A. J. R., Behjati, S., Biankin, A. V., et al. (2013) · Nature · doi:10.1038/nature12477 · Cited by 9,660 · see citing works
Self-citationAnalysis of protein-coding genetic variation in 60,706 humans
Exome Aggregation Consortium, Lek, M., Karczewski, K. J., Minikel, E. V., Samocha, K. E., Banks, E., Fennell, T., O’Donnell-Luria, A. H., Ware, J. S., Hill, A. J., et al. (2016) · Nature · doi:10.1038/nature19057 · Cited by 9,587 · see citing works
Vogelstein, B., Papadopoulos, N., Velculescu, V. E., Zhou, S., Diaz, L. A., & Kinzler, K. W. (2013) · Science · doi:10.1126/science.1235122 · Cited by 7,863 · see citing works
dbSNP: the NCBI database of genetic variation
Sherry, S. T. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.1.308 · Cited by 7,502 · see citing works
Nowell, P. C. (1976) · Science · doi:10.1126/science.959840 · Cited by 6,471 · see citing works
Integrative analysis of 111 reference human epigenomes
Roadmap Epigenomics Consortium, Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., Kheradpour, P., Zhang, Z., Wang, J., et al. (2015) · Nature · doi:10.1038/nature14248 · Cited by 6,368 · see citing works
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 · see citing works
Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions.
Nei, M., & Gojobori, T. (1986) · Molecular Biology and Evolution · doi:10.1093/oxfordjournals.molbev.a040410 · Cited by 4,904 · see citing works
Mutational landscape and significance across 12 major cancer types
Kandoth, C., McLellan, M. D., Vandin, F., Ye, K., Niu, B., Lu, C., Xie, M., Zhang, Q., McMichael, J. F., Wyczalkowski, M. A., et al. (2013) · Nature · doi:10.1038/nature12634 · Cited by 4,419 · see citing works
Molecular and genetic properties of tumors associated with local immune cytolytic activity
Rooney, M. S., Shukla, S. A., Wu, C. J., Getz, G., & Hacohen, N. (2015) · Cell · doi:10.1016/j.cell.2014.12.033 · Cited by 3,825 · see citing works
Discovery and saturation analysis of cancer genes across 21 tumour types
Lawrence, M. S., Stojanov, P., Mermel, C. H., Robinson, J. T., Garraway, L. A., Golub, T. R., Meyerson, M., Gabriel, S. B., Lander, E. S., & Getz, G. (2014) · Nature · doi:10.1038/nature12912 · Cited by 3,096 · cited 10× · see citing works
“For example, MutSigCV uses three covariates to estimate the mutation rate of each gene, by using information from other genes with similar covariate values (Lawrence et al., 2014; Lawrence et al., 2013).”
InfluentialClonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade
McGranahan, N., Furness, A. J. S., Rosenthal, R., Ramskov, S., Lyngaa, R., Saini, S. K., Jamal-Hanjani, M., Wilson, G. A., Birkbak, N. J., Hiley, C. T., et al. (2016) · Science · doi:10.1126/science.aaf1490 · Cited by 3,065 · see citing works
Patterns 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 · see citing works
Self-citationCOSMIC: exploring the world's knowledge of somatic mutations in human cancer
Forbes, S. A., Beare, D. M., Gunasekaran, P., Leung, K., Bindal, N., Boutselakis, H., Ding, M., Bamford, S., Cole, C. G., Ward, S. A., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku1075 · Cited by 2,261 · see citing works
Self-citationLandscape of somatic mutations in 560 breast cancer whole-genome sequences
Nik-Zainal, S., Davies, H., Staaf, J., Ramakrishna, M., Glodzik, D., Zou, X., Martincorena, I., Alexandrov, L. B., Martin, S., Wedge, D. C., et al. (2016) · Nature · doi:10.1038/nature17676 · Cited by 2,218 · see citing works
Self-citationA codon-based model of nucleotide substitution for protein-coding DNA sequences.
(1994) · Molecular Biology and Evolution · doi:10.1093/oxfordjournals.molbev.a040153 · Cited by 1,960 · see citing works
Age-related mutations associated with clonal hematopoietic expansion and malignancies
Xie, M., Lu, C., Wang, J., McLellan, M. D., Johnson, K. J., Wendl, M. C., McMichael, J. F., Schmidt, H. K., Yellapantula, V., Miller, C. A., et al. (2014) · Nature Medicine · doi:10.1038/nm.3733 · Cited by 1,874 · see citing works
Statistical methods for detecting molecular adaptation
Yang, Z., & Bielawski, J. P. (2000) · Trends in Ecology & Evolution · doi:10.1016/s0169-5347(00)01994-7 · Cited by 1,807 · see citing works
Wang, K., Li, M., Hadley, D., Liu, R., Glessner, J., Grant, S. F. A., Hakonarson, H., & Bucan, M. (2007) · Genome Research · doi:10.1101/gr.6861907 · Cited by 1,792 · see citing works
High burden and pervasive positive selection of somatic mutations in normal human skin
Martincorena, I., Roshan, A., Gerstung, M., Ellis, P., Van Loo, P., McLaren, S., Wedge, D. C., Fullam, A., Alexandrov, L. B., Tubio, J. M., et al. (2015) · Science · doi:10.1126/science.aaa6806 · Cited by 1,770 · see citing works
Self-citationEstimating Synonymous and Nonsynonymous Substitution Rates Under Realistic Evolutionary Models
Yang, Z., & Nielsen, R. (2000) · Molecular Biology and Evolution · doi:10.1093/oxfordjournals.molbev.a026236 · Cited by 1,747 · 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-citationNielsen, R., & Yang, Z. (1998) · Genetics · doi:10.1093/genetics/148.3.929 · Cited by 1,622 · see citing works
Mutation selection and the natural history of cancer
Cairns, J. (1975) · Nature · doi:10.1038/255197a0 · Cited by 1,592 · see citing works
The origin and evolution of mutations in acute myeloid leukemia
Welch, J. S., Ley, T. J., Link, D. C., Miller, C. A., Larson, D. E., Koboldt, D. C., Wartman, L. D., Lamprecht, T. L., Liu, F., Xia, J., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.023 · Cited by 1,575 · see citing works
The Age Distribution of Cancer and a Multi-stage Theory of Carcinogenesis
Armitage, P., & Doll, R. (1954) · British Journal of Cancer · doi:10.1038/bjc.1954.1 · Cited by 1,549 · see citing works
Somatic 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-citationThe age distribution of cancer and a multi-stage theory of carcinogenesis
Armitage, P., & Doll, R. (2004) · British Journal of Cancer · doi:10.1038/sj.bjc.6602297 · Cited by 1,309 · see citing works
Allele-specific copy number analysis of tumors
Loo, P. V., Nord, S., Lingjærde, O. C., Russnes, H. G., Rye, I. H., Sun, W., Weigman, V., Marynen, P., Zetterberg, A., Naume, B., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1009843107 · Cited by 1,231 · 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-citationClassification and characterization of microsatellite instability across 18 cancer types
Hause, R. J., Pritchard, C. C., Shendure, J., & Salipante, S. J. (2016) · Nature Medicine · doi:10.1038/nm.4191 · Cited by 982 · see citing works
The Population Genetics of dN/dS
Kryazhimskiy, S., & Plotkin, J. B. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000304 · Cited by 962 · see citing works
Tissue-specific mutation accumulation in human adult stem cells during life
Blokzijl, F., de Ligt, J., Jager, M., Sasselli, V., Roerink, S., Sasaki, N., Huch, M., Boymans, S., Kuijk, E., Prins, P., et al. (2016) · Nature · doi:10.1038/nature19768 · Cited by 935 · see citing works
Self-citationHeterogeneity 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-citationGene essentiality and synthetic lethality in haploid human cells
Blomen, V. A., Májek, P., Jae, L. T., Bigenzahn, J. W., Nieuwenhuis, J., Staring, J., Sacco, R., van Diemen, F. R., Olk, N., Stukalov, A., et al. (2015) · Science · doi:10.1126/science.aac7557 · Cited by 857 · see citing works
Davoli, T., Xu, A. W., Mengwasser, K. E., Sack, L. M., Yoon, J. C., Park, P. J., & Elledge, S. J. (2013) · Cell · doi:10.1016/j.cell.2013.10.011 · Cited by 815 · see citing works
Subclonal diversification of primary breast cancer revealed by multiregion sequencing
Yates, L. R., Gerstung, M., Knappskog, S., Desmedt, C., Gundem, G., Loo, P. V., Aas, T., Alexandrov, L. B., Larsimont, D., Davies, H., et al. (2015) · Nature Medicine · doi:10.1038/nm.3886 · Cited by 812 · see citing works
Self-citationA New Theory on the Cancer-inducing Mechanism
Nordling, C. O. (1953) · British Journal of Cancer · doi:10.1038/bjc.1953.8 · Cited by 779 · see citing works
Chromatin organization is a major influence on regional mutation rates in human cancer cells
Schuster-Böckler, B., & Lehner, B. (2012) · Nature · doi:10.1038/nature11273 · Cited by 657 · cited 4× · see citing works
“…a statistical model ( dNdScv ) that combines the local observed synonymous mutation rate with a regression model using covariates that predict the variable mutation rate across the genome (Lawrence et al., 2013; Polak et al., 2015; Schuster-Bockler and Lehner, 2012) (Supplementary Methods S1.”
InfluentialCell-of-origin chromatin organization shapes the mutational landscape of cancer
Polak, P., Karlić, R., Koren, A., Thurman, R., Sandstrom, R., Lawrence, M. S., Reynolds, A., Rynes, E., Vlahoviček, K., Stamatoyannopoulos, J. A., et al. (2015) · Nature · doi:10.1038/nature14221 · Cited by 557 · see citing works
Synonymous mutations frequently act as driver mutations in human cancers.
Supek, F., Miñana, B., Valcárcel, J., Gabaldón, T., & Lehner, B. (2014) · Cell · doi:10.1016/j.cell.2014.01.051 · Cited by 553 · see citing works
The mutation spectrum revealed by paired genome sequences from a lung cancer patient
Lee, W., Jiang, Z., Liu, J., Haverty, P. M., Guan, Y., Stinson, J., Yue, P., Zhang, Y., Pant, K. P., Bhatt, D., et al. (2010) · Nature · doi:10.1038/nature09004 · Cited by 486 · see citing works
Targeting of cancer neoantigens with donor-derived T cell receptor repertoires
Strønen, E., Toebes, M., Kelderman, S., van Buuren, M. M., Yang, W., van Rooij, N., Donia, M., Böschen, M.-L., Lund‐Johansen, F., Olweus, J., et al. (2016) · Science · doi:10.1126/science.aaf2288 · Cited by 443 · see citing works
Miyata, T., & Yasunaga, T. (1980) · Journal of Molecular Evolution · doi:10.1007/bf01732067 · Cited by 411 · see citing works
Only three driver gene mutations are required for the development of lung and colorectal cancers
Tomasetti, C., Marchionni, L., Nowak, M. A., Parmigiani, G., & Vogelstein, B. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1421839112 · Cited by 395 · see citing works
Mutational Strand Asymmetries in Cancer Genomes Reveal Mechanisms of DNA Damage and Repair
Haradhvala, N. J., Polak, P. P., Stojanov, P., Covington, K. R., Shinbrot, E., Hess, J. M., Rheinbay, E., Kim, J., Maruvka, Y. E., Braunstein, L. Z., et al. (2016) · Cell · doi:10.1016/j.cell.2015.12.050 · Cited by 387 · see citing works
Shlien, A., Campbell, B. B., de Borja, R., Alexandrov, L. B., Merico, D., Wedge, D. C., Loo, P. V., Tarpey, P. S., Coupland, P. G., Behjati, S., et al. (2015) · Nature Genetics · doi:10.1038/ng.3202 · Cited by 374 · see citing works
Self-citationA panoply of errors: polymerase proofreading domain mutations in cancer
Rayner, E., van Gool, I. C., Palles, C., Kearsey, S. E., Bosse, T., Tomlinson, I. P. M., & Church, D. N. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2015.12 · Cited by 371 · see citing works
DNA polymerase ɛ and δ exonuclease domain mutations in endometrial cancer
Church, D. N., Briggs, S., Palles, C., Domingo, E., Kearsey, S. J., Grimes, J. M., Gorman, M., Martin, L. M., Howarth, K. M., Hodgson, S. V., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt131 · Cited by 354 · see citing works
Mularoni, L., Sabarinathan, R., Deu-Pons, J., González-Pérez, A., & López-Bigas, N. (2016) · Genome biology · doi:10.1186/s13059-016-0994-0 · Cited by 323 · see citing works
Systematic identification of personal tumor-specific neoantigens in chronic lymphocytic leukemia
Rajasagi, M., Shukla, S. A., Fritsch, E. F., Keskin, D. B., DeLuca, D. S., Carmona, E. M., Zhang, W., Sougnez, C. L., Cibulskis, K., Sidney, J., et al. (2014) · Blood · doi:10.1182/blood-2014-04-567933 · Cited by 309 · see citing works
Impact of deleterious passenger mutations on cancer progression
McFarland, C. D., Korolev, K. S., Kryukov, G. V., Sunyaev, S. R., & Mirny, L. A. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1213968110 · Cited by 307 · see citing works
Rubio-Perez, C., Tamborero, D., Schroeder, M. P., Antolín, A. A., Deu-Pons, J., Perez-Llamas, C., Mestres, J., Gonzalez-Perez, A., & Lopez-Bigas, N. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.02.007 · Cited by 296 · see citing works
Fredriksson, N. J., Ny, L., Nilsson, J. A., & Larsson, E. (2014) · Nature Genetics · doi:10.1038/ng.3141 · Cited by 282 · see citing works
Precision oncology for acute myeloid leukemia using a knowledge bank approach
Gerstung, M., Papaemmanuil, E., Martin, S., Bullinger, L., Gaidzik, V. I., Paschka, P., Heuser, M., Thol, F. R., Bolli, N., Ganly, P. S., et al. (2017) · Nature Genetics · doi:10.1038/ng.3756 · Cited by 275 · see citing works
Self-citationJones, D., Raine, K. M., Davies, H. R., Tarpey, P. S., Butler, A. P., Teague, J. W., Nik‐Zainal, S., & Campbell, P. J. (2016) · Current Protocols in Bioinformatics · doi:10.1002/cpbi.20 · Cited by 227 · see citing works
Self-citationEvidence of non-random mutation rates suggests an evolutionary risk management strategy
Martincorena, I., Seshasayee, A. S. N., & Luscombe, N. M. (2012) · Nature · doi:10.1038/nature10995 · Cited by 215 · see citing works
Self-citationRNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence
Galloway, A., Saveliev, A., Łukasiak, S., Hodson, D. J., Bolland, D. J., Balmanno, K., Ahlfors, H., Monzón‐Casanova, E., Mannurita, S. C., Bell, L. S., et al. (2016) · Science · doi:10.1126/science.aad5978 · Cited by 176 · see citing works
ascatNgs: Identifying Somatically Acquired Copy‐Number Alterations from Whole‐Genome Sequencing Data
Raine, K. M., Loo, P. V., Wedge, D. C., Jones, D., Menzies, A. H., Butler, A. P., Teague, J. W., Tarpey, P. S., Nik‐Zainal, S., & Campbell, P. J. (2016) · Current Protocols in Bioinformatics · doi:10.1002/cpbi.17 · Cited by 170 · see citing works
Self-citationStatistical 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 · see citing works
Self-citationTug-of-war between driver and passenger mutations in cancer and other adaptive processes
McFarland, C. D., Mirny, L. A., & Korolev, K. S. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1404341111 · Cited by 156 · see citing works
Subclonal variant calling with multiple samples and prior knowledge
Gerstung, M., Papaemmanuil, E., & Campbell, P. J. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btt750 · Cited by 154 · see citing works
Self-citationcgpPindel: Identifying Somatically Acquired Insertion and Deletion Events from Paired End Sequencing
Raine, K. M., Hinton, J., Butler, A. P., Teague, J. W., Davies, H. R., Tarpey, P. S., Nik‐Zainal, S., & Campbell, P. J. (2015) · Current Protocols in Bioinformatics · doi:10.1002/0471250953.bi1507s52 · Cited by 141 · see citing works
Self-citationInactivating CUX1 mutations promote tumorigenesis
Wong, C. C., Martin, S., Rust, A. G., Rashid, M., Alifrangis, C., Alexandrov, L. B., Tiffen, J. C., Kober, C., Green, A. R., Massie, C. E., et al. (2013) · Nature Genetics · doi:10.1038/ng.2846 · Cited by 132 · see citing works
Self-citationThe mini-driver model of polygenic cancer evolution
Castro-Giner, F., Ratcliffe, P. J., & Tomlinson, I. P. M. (2015) · Nature reviews. Cancer · doi:10.1038/nrc3999 · Cited by 129 · see citing works
Dias, J. C., Nguyen, N. V., Georgiev, P., Gaub, A., Brettschneider, J., Cusack, S., Kadlec, J., & Akhtar, A. (2014) · Genes & Development · doi:10.1101/gad.240200.114 · Cited by 115 · see citing works
Lee, H., Palm, J., Grimes, S. M., & Ji, H. P. (2015) · Genome Medicine · doi:10.1186/s13073-015-0226-3 · Cited by 111 · see citing works
Cancer Evolution Is Associated with Pervasive Positive Selection on Globally Expressed Genes
Ostrow, S. L., Barshir, R., DeGregori, J. V., Yeger‐Lotem, E., & Hershberg, R. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004239 · Cited by 100 · see citing works
The somatic mutation theory of ageing
Morley, A. A. (1995) · Mutation Research/DNAging · doi:10.1016/0921-8734(95)00007-s · Cited by 66 · see citing works
Negative Clonal Selection in Tumor Evolution
Beckman, R. A., & Loeb, L. A. (2005) · Genetics · doi:10.1534/genetics.105.040840 · Cited by 42 · see citing works
Likelihood Models of Somatic Mutation and Codon Substitution in Cancer Genes
Yang, Z., Ro, S. W., & Rannala, B. H. (2003) · Genetics · doi:10.1093/genetics/165.2.695 · Cited by 40 · see citing works
den Eynden, J. V., Basu, S., & Larsson, E. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006506 · Cited by 32 · see citing works
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Self-citationHayes, J. D., Dinkova-Kostova, A. T., & Tew, K. D. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.06.001 · Cited by 2,654 · see citing works
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Pan-cancer whole-genome analyses of metastatic solid tumours
Priestley, P., Baber, J., Lolkema, M. P., Steeghs, N., de Bruijn, E., Shale, C., Duyvesteyn, K., Haidari, S., van Hoeck, A., Onstenk, W., et al. (2019) · Nature · doi:10.1038/s41586-019-1689-y · Cited by 1,106 · see citing works
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Lee-Six, H., Olafsson, S., Ellis, P., Osborne, R. J., Sanders, M. A., Moore, L., Georgakopoulos, N., Torrente, F., Noorani, A., Goddard, M., et al. (2019) · Nature · doi:10.1038/s41586-019-1672-7 · Cited by 747 · see citing works
Self-citationEvidence for 28 genetic disorders discovered by combining healthcare and research data
Kaplanis, J., Samocha, K. E., Wiel, L., Zhang, Z., Arvai, K. J., Eberhardt, R. Y., Gallone, G., Lelieveld, S. H., Martin, H. C., McRae, J. F., et al. (2020) · Nature · doi:10.1038/s41586-020-2832-5 · Cited by 615 · see citing works
Self-citationChakravarthy, A., Khan, L., Bensler, N. P., Bose, P., & De Carvalho, D. D. (2018) · Nature Communications · doi:10.1038/s41467-018-06654-8 · Cited by 656 · see citing works
Population dynamics of normal human blood inferred from somatic mutations
Lee-Six, H., Øbro, N. F., Shepherd, M. S., Grossmann, S., Dawson, K., Belmonte, M., Osborne, R. J., Huntly, B. J. P., Martincorena, I., Anderson, E., et al. (2018) · Nature · doi:10.1038/s41586-018-0497-0 · Cited by 604 · see citing works
Self-citationAge-related remodelling of oesophageal epithelia by mutated cancer drivers
Yokoyama, A., Kakiuchi, N., Yoshizato, T., Nannya, Y., Suzuki, H., Takeuchi, Y., Shiozawa, Y., Sato, Y., Aoki, K., Kim, S. K., et al. (2019) · Nature · doi:10.1038/s41586-018-0811-x · Cited by 628 · see citing works
The hallmarks of successful anticancer immunotherapy
Galluzzi, L., Chan, T. A., Kroemer, G., Wolchok, J. D., & López-Soto, A. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aat7807 · Cited by 575 · see citing works
Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes
Dentro, S. C., Leshchiner, I., Haase, K., Tarabichi, M., Wintersinger, J., Deshwar, A. G., Yu, K., Rubanova, Y., Macintyre, G., Demeulemeester, J., et al. (2021) · Cell · doi:10.1016/j.cell.2021.03.009 · Cited by 533 · see citing works
Self-citationThe mutational landscape of normal human endometrial epithelium
Moore, L., Leongamornlert, D., Coorens, T. H. H., Sanders, M. A., Ellis, P., Dentro, S. C., Dawson, K. J., Butler, T., Rahbari, R., Mitchell, T. J., et al. (2020) · Nature · doi:10.1038/s41586-020-2214-z · Cited by 499 · see citing works
Self-citationIn vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels
Rothgangl, T., Dennis, M. K., Lin, P. J. C., Oka, R., Witzigmann, D., Villiger, L., Qi, W., Hruzova, M., Kissling, L., Lenggenhager, D., et al. (2021) · Nature Biotechnology · doi:10.1038/s41587-021-00933-4 · Cited by 378 · see citing works
Immunological impact of cell death signaling driven by radiation on the tumor microenvironment
Rodriguez-Ruiz, M. E., Vitale, I., Harrington, K. J., Melero, I., & Galluzzi, L. (2020) · Nature Immunology · doi:10.1038/s41590-019-0561-4 · Cited by 385 · see citing works
Interleukin-22 protects intestinal stem cells against genotoxic stress
Gronke, K., Hernández, P. P., Zimmermann, J., Klose, C. S. N., Kofoed-Branzk, M., Guendel, F., Witkowski, M., Tizian, C., Amann, L., Schumacher, F., et al. (2019) · Nature · doi:10.1038/s41586-019-0899-7 · Cited by 373 · see citing works
Pan-cancer deconvolution of tumour composition using DNA methylation
Chakravarthy, A., Furness, A., Joshi, K., Ghorani, E., Ford, K., Ward, M. J., King, E. V., Lechner, M., Marafioti, T., Quezada, S. A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05570-1 · Cited by 327 · see citing works
Extensive heterogeneity in somatic mutation and selection in the human bladder
Lawson, A. R. J., Abascal, F., Coorens, T. H. H., Hooks, Y., O’Neill, L., Latimer, C., Raine, K., Sanders, M. A., Warren, A. Y., Mahbubani, K. T. A., et al. (2020) · Science · doi:10.1126/science.aba8347 · Cited by 311 · see citing works
Self-citationNoorbakhsh, J., Farahmand, S., Foroughi pour, A., Namburi, S., Caruana, D., Rimm, D., Soltanieh-ha, M., Zarringhalam, K., & Chuang, J. H. (2020) · Nature Communications · doi:10.1038/s41467-020-20030-5 · Cited by 206 · see citing works
Macroscopic somatic clonal expansion in morphologically normal human urothelium
Li, R., Du, Y., Chen, Z., Xu, D., Lin, T., Jin, S., Wang, G., Liu, Z., Lu, M., Chen, X., et al. (2020) · Science · doi:10.1126/science.aba7300 · Cited by 206 · 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-citationIncreased somatic mutation burdens in normal human cells due to defective DNA polymerases
Robinson, P. S., Coorens, T. H. H., Palles, C., Mitchell, E., Abascal, F., Olafsson, S., Lee, B. C. H., Lawson, A. R. J., Lee-Six, H., Moore, L., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00930-y · Cited by 173 · see citing works
Self-citationAn integrative ENCODE resource for cancer genomics
Zhang, J., Lee, D., Dhiman, V., Jiang, P., Xu, J., McGillivray, P., Yang, H., Liu, J., Meyerson, W., Clarke, D., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14743-w · Cited by 172 · see citing works
Integrative proteogenomic characterization of hepatocellular carcinoma across etiologies and stages
Ng, C. K. Y., Dazert, E., Boldanova, T., Coto-Llerena, M., Nuciforo, S., Ercan, C., Suslov, A., Meier, M.-A., Bock, T., Schmidt, A., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29960-8 · Cited by 165 · see citing works
Huang, Z., Sun, S., Lee, M., Maslov, A. Y., Shi, M., Waldman, S., Marsh, A., Siddiqui, T., Dong, X., Peter, Y., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01035-w · Cited by 125 · see citing works
Genomic Classification and Individualized Prognosis in Multiple Myeloma
Maura, F., Rajanna, A. R., Ziccheddu, B., Poos, A. M., Derkach, A., Maclachlan, K., Durante, M., Diamond, B., Papadimitriou, M., Davies, F., et al. (2024) · Journal of Clinical Oncology · doi:10.1200/jco.23.01277 · Cited by 131 · see citing works
Pich, O., Muiños, F., Sabarinathan, R., Reyes-Salazar, I., Gonzalez-Perez, A., & Lopez-Bigas, N. (2018) · Cell · doi:10.1016/j.cell.2018.10.004 · Cited by 123 · see citing works
Rouhani, F. J., Zou, X., Danecek, P., Badja, C., Amarante, T. D., Koh, G., Wu, Q., Memari, Y., Durbin, R., Martincorena, I., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01147-3 · Cited by 105 · see citing works
Integrating the DNA damage and protein stress responses during cancer development and treatment
Gorgoulis, V. G., Pefani, D., Pateras, I. S., & Trougakos, I. P. (2018) · The Journal of Pathology · doi:10.1002/path.5097 · Cited by 108 · see citing works
Cancer-associated mutations in endometriosis: shedding light on the pathogenesis and pathophysiology
Guo, S.-W. (2020) · Human Reproduction Update · doi:10.1093/humupd/dmz047 · Cited by 96 · see citing works
Jain, M. D., Ziccheddu, B., Coughlin, C. A., Faramand, R., Griswold, A. J., Reid, K. M., Menges, M., Zhang, Y., Cen, L., Wang, X., et al. (2022) · Blood · doi:10.1182/blood.2021015008 · Cited by 91 · see citing works
Genome-wide mapping of somatic mutation rates uncovers drivers of cancer
Sherman, M. A., Yaari, A. U., Priebe, O., Dietlein, F., Loh, P.-R., & Berger, B. (2022) · Nature Biotechnology · doi:10.1038/s41587-022-01353-8 · Cited by 80 · see citing works
Selfish mutations dysregulating RAS-MAPK signaling are pervasive in aged human testes
Maher, G. J., Ralph, H. K., Ding, Z., Koelling, N., Mlcochova, H., Giannoulatou, E., Dhami, P., Paul, D. S., Stricker, S. H., Beck, S., et al. (2018) · Genome Research · doi:10.1101/gr.239186.118 · Cited by 85 · see citing works
Contribution of pks+ E. coli mutations to colorectal carcinogenesis
Chen, B., Ramazzotti, D., Heide, T., Spiteri, I., Fernandez-Mateos, J., James, C., Magnani, L., Graham, T. A., & Sottoriva, A. (2023) · Nature Communications · doi:10.1038/s41467-023-43329-5 · Cited by 74 · see citing works
“We performed the inference on a joint cohort comprising tumour samples from our dataset of cancer patients and normal crypts from normal people 8 .”
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-citationSanchez-Contreras, M., Sweetwyne, M. T., Tsantilas, K. A., Whitson, J. A., Campbell, M. D., Kohrn, B. F., Kim, H. J., Hipp, M. J., Fredrickson, J., Nguyen, M. M., et al. (2023) · eLife · doi:10.7554/elife.83395 · Cited by 71 · see citing works
Kaplanis, J., Samocha, K. E., Wiel, L., Zhang, Z., Arvai, K. J., Eberhardt, R. Y., Gallone, G., Lelieveld, S. H., Martin, H. C., McRae, J. F., et al. (2019) · doi:10.1101/797787 · Cited by 36 · see citing works
Self-citationHuang, A. Y., Zhou, Z., Talukdar, M., Enyenihi, L., Miller, M. B., Chhouk, B., Rosen, I., Zheng, M., Zhou, M., Yang, A., et al. (2026) · Cell · doi:10.1016/j.cell.2026.03.040 · Cited by 15 · see citing works
Brzozowska, N., Wu, L. Y. D., Khodzhaeva, V., Griffiths, W. J., Duckworth, A., Jung, H., Coorens, T. H. H., Hooks, Y., Chambers, J. E., Campbell, P. J., et al. (2025) · Nature Genetics · doi:10.1038/s41588-025-02125-1 · Cited by 11 · see citing works
Self-citation
- Authors
- Martincorena, I., Raine, K. M., Gerstung, M., Dawson, K. J., Haase, K., Van Loo, P., Davies, H., Stratton, M. R., & Campbell, P. J.
- Affiliations
- Wellcome Sanger Institute (GB)
- European Bioinformatics Institute (GB)
- The Francis Crick Institute (GB)
- University of Cambridge (GB)
- Corresponding author
- Martincorena, Iñigo
- Campbell, Peter J.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2017-11
- Volume
- 171
- Issue
- 5
- Pages
- 1029-1041.e21
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5720395
- OpenAlex
- W2611387862
- Cited by
- 1,523
- References
- 75
- Citations by year
- 2026: 109 · 2025: 171 · 2024: 192 · 2023: 215 · 2022: 206 · 2021: 183 · 2020: 183 · 2019: 147 · 2018: 105 · 2017: 11
- FWCI
- 41.02
- Type
- journal article
- Language
- en
- Update notices
- erratum (2018-06-14)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- EMBO (766-2015)
- Cancer Research UK (C57387/A21777, FC001202)
- Wellcome Trust (FC001202)
- Francis Crick Institute
- UK Medical Research Council (FC001202)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- tumor evolution, clonal selection, positive selection, negative selection, purifying selection, driver mutations, passenger mutations, somatic mutations, mutational burden, cancer genes
- MeSH terms
- Humans, Models, Genetic, Neoplasms, Selection, Genetic, Point Mutation, Polymorphism, Single Nucleotide, Microsatellite Instability, INDEL Mutation, Mutation Rate
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