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Cited by 3,496Cancer Genomics and DiagnosticsChromatin Remodeling and CancerDNA Repair Mechanisms

The repertoire of mutational signatures in human cancer

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Alexandrov, Ludmil B., Kim, Jaegil, Haradhvala, Nicholas J., Huang, Mi Ni, Tian Ng, Alvin Wei, Wu, Yang, Boot, Arnoud, Covington, Kyle R. +1377 more·2020·Nature
DOI 10.1038/s41586-020-1943-3PMC PMC7054213

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Abstract

Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature 1 . Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium 2 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we characterized mutational signatures using 84,729,690 somatic mutations from 4,645 whole-genome and 19,184 exome sequences that encompass most types of cancer. We identified 49 single-base-substitution, 11 doublet-base-substitution, 4 clustered-base-substitution and 17 small insertion-and-deletion signatures. The substantial size of our dataset, compared with previous analyses 3–15 , enabled the discovery of new signatures, the separation of overlapping signatures and the decomposition of signatures into components that may represent associated—but distinct—DNA damage, repair and/or replication mechanisms. By estimating the contribution of each signature to the mutational catalogues of individual cancer genomes, we revealed associations of signatures to exogenous or endogenous exposures, as well as to defective DNA-maintenance processes. However, many signatures are of unknown cause. This analysis provides a systematic perspective on the repertoire of mutational processes that contribute to the development of human cancer.

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Crossref · 10.1038/s41586-020-1943-3

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  • To assess the genome-wide off-target effects of base editor activity in intestinal organoids, we compared culture-related (SBS1, SBS5, SBS18), as well as APOBEC-related (SBS2, SBS13) mutational signatures to the overall mutational profile using the Bioconductor R package MutationalPatterns v.3.2.0.

    “To assess the genome-wide off-target effects of base editor activity in intestinal organoids, we compared culture-related (SBS1, SBS5, SBS18), as well as APOBEC-related (SBS2, SBS13) mutational signatures to the overall mutational profile using the Bioconductor R package MutationalPatterns v.3.2.056,58,59.”

    From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [56]

    The Single-base substitution signatures section identifies SBS2 and SBS13 as APOBEC-related, supporting that part of the signature selection. The Correlations with age section links SBS1 and SBS5 to age, but our copy does not identify SBS1, SBS5 and SBS18 as culture-related signatures. The organoid comparison and software use describe the citing authors’ own method, not a finding attributed to this source. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • SBS2 and SBS13 have been associated with APOBEC activity in cancer and can be explained by APOBEC1A bound to Cas9 in CBE architecture.

    “The other signatures, SBS2 and SBS13, has been associated with APOBEC activity in cancer56 and can be explained by the APOBEC1A bound to Cas9 in the CBE architecture.”

    From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [56]

  • These genomic features include the presence of COSMIC mutational signature 3, possibly representing defective DNA damage response in osteosarcoma, in ~30% of cases, and frequent genomic events that lead to replication stress such as MYC amplification and CCNE1 amplification.

    “These features include the presence of COSMIC mutational signature 3 (ref. 154 ), possibly representing defective DNA damage response in osteosarcoma, in ~30% of cases, and the frequent presence of genomic events that lead to replication stress such as MYC amplification and CCNE1 amplification.”

    From Osteosarcoma (2022) · cites this paper as [154]

  • The mutational signature AC3 identifies MSS cancers with homologous recombination repair deficiency.

    “The mutational signature AC3 identifies MSS cancers with homologous recombination repair deficiency (Alexandrov et al., 2020).”

    From Degradation of CCNK/CDK12 is a druggable vulnerability of colorectal cancer (2021) · cites this paper as Alexandrov et al., 2020

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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., Islam, S. M. A., Lopez-Bigas, N., Klimczak, L. J., McPherson, J. R., Morganella, S., Sabarinathan, R., Wheeler, D. A., Mustonen, V., PCAWG Mutational Signatures Working Group, Alexandrov, L. B., Bergstrom, E. N., Boot, A., Boutros, P., Chan, K., Covington, K. R., Fujimoto, A., Getz, G., Gordenin, D. A., Haradhvala, N. J., Huang, M. N., Islam, S. M. A., Kazanov, M., Kim, J., Klimczak, L. J., Lopez-Bigas, N., Lawrence, M., Martincorena, I., McPherson, J. R., Morganella, S., Mustonen, V., Nakagawa, H., Tian Ng, A. W., Polak, P., Prokopec, S., Roberts, S. A., Rozen, S. G., Sabarinathan, R., Saini, N., Shibata, T., Shiraishi, Y., Stratton, M. R., Teh, B. T., Vázquez-García, I., Wheeler, D. A., Wu, Y., Yousif, F., Yu, W., Getz, G., Rozen, S. G., Stratton, M. R., PCAWG Consortium, Aaltonen, L. A., Abascal, F., Abeshouse, A., Aburatani, H., Adams, D. J., Agrawal, N., Ahn, K. S., Ahn, S.-M., Aikata, H., Akbani, R., Akdemir, K. C., Al-Ahmadie, H., Al-Sedairy, S. T., Al-Shahrour, F., Alawi, M., Albert, M., Aldape, K., Alexandrov, L. B., Ally, A., Alsop, K., Alvarez, E. G., Amary, F., Amin, S. B., Aminou, B., Ammerpohl, O., Anderson, M. J., Ang, Y., Antonello, D., Anur, P., Aparicio, S., Appelbaum, E. L., Arai, Y., Aretz, A., Arihiro, K., Ariizumi, S.-I., Armenia, J., Arnould, L., Asa, S., Assenov, Y., Atwal, G., Aukema, S., Auman, J. T., Aure, M. R. R., Awadalla, P., Aymerich, M., Bader, G. D., Baez-Ortega, A., Bailey, M. H., Bailey, P. J., Balasundaram, M., Balu, S., Bandopadhayay, P., Banks, R. E., Barbi, S., Barbour, A. P., Barenboim, J., Barnholtz-Sloan, J., Barr, H., Barrera, E., Bartlett, J., Bartolome, J., Bassi, C., Bathe, O. F., Baumhoer, D., Bavi, P., Baylin, S. B., Bazant, W., Beardsmore, D., Beck, T. A., Behjati, S., Behren, A., Niu, B., Bell, C., Beltran, S., Benz, C., Berchuck, A., Bergmann, A. K., Bergstrom, E. N., Berman, B. P., Berney, D. M., Bernhart, S. H., Beroukhim, R., Berrios, M., Bersani, S., Bertl, J., Betancourt, M., Bhandari, V., Bhosle, S. G., Biankin, A. V., Bieg, M., Bigner, D., Binder, H., Birney, E., Birrer, M., Biswas, N. K., Bjerkehagen, B., Bodenheimer, T., Boice, L., Bonizzato, G., De Bono, J. S., Boot, A., Bootwalla, M. S., Borg, A., Borkhardt, A., Boroevich, K. A., Borozan, I., Borst, C., Bosenberg, M., Bosio, M., Boultwood, J., Bourque, G., Boutros, P. C., Bova, G. S., Bowen, D. T., Bowlby, R., Bowtell, D. D. L., Boyault, S., Boyce, R., Boyd, J., Brazma, A., Brennan, P., Brewer, D. S., Brinkman, A. B., Bristow, R. G., Broaddus, R. R., Brock, J. E., Brock, M., Broeks, A., Brooks, A. N., Brooks, D., Brors, B., Brunak, S., Bruxner, T. J. C., Bruzos, A. L., Buchanan, A., Buchhalter, I., Buchholz, C., Bullman, S., Burke, H., Burkhardt, B., Burns, K. H., Busanovich, J., Bustamante, C. D., Butler, A. P., Butte, A. J., Byrne, N. J., Børresen-Dale, A.-L., Caesar-Johnson, S. J., Cafferkey, A., Cahill, D., Calabrese, C., Caldas, C., Calvo, F., Camacho, N., Campbell, P. J., Campo, E., Cantù, C., Cao, S., Carey, T. E., Carlevaro-Fita, J., Carlsen, R., Cataldo, I., Cazzola, M., Cebon, J., Cerfolio, R., Chadwick, D. E., Chakravarty, D., Chalmers, D., Chan, C. W. Y., Chan, K., Chan-Seng-Yue, M., Chandan, V. S., Chang, D. K., Chanock, S. J., Chantrill, L. A., Chateigner, A., Chatterjee, N., Chayama, K., Chen, H.-W., Chen, J., Chen, K., Chen, Y., Chen, Z., Cherniack, A. D., Chien, J., Chiew, Y.-E., Chin, S.-F., Cho, J., Cho, S., Choi, J. K., Choi, W., Chomienne, C., Chong, Z., Choo, S. P., Chou, A., Christ, A. N., Christie, E. L., Chuah, E., Cibulskis, C., Cibulskis, K., Cingarlini, S., Clapham, P., Claviez, A., Cleary, S., Cloonan, N., Cmero, M., Collins, C. C., Connor, A. A., Cooke, S. L., Cooper, C. S., Cope, L., Corbo, V., Cordes, M. G., Cordner, S. M., Cortés-Ciriano, I., Covington, K., Cowin, P. A., Craft, B., Craft, D., Creighton, C. J., Cun, Y., Curley, E., Cutcutache, I., Czajka, K., Czerniak, B., Dagg, R. A., Danilova, L., Davi, M. V., Davidson, N. R., Davies, H., Davis, I. J., Davis-Dusenbery, B. N., Dawson, K. J., De La Vega, F. M., De Paoli-Iseppi, R., Defreitas, T., Tos, A. P. D., Delaneau, O., Demchok, J. A., Demeulemeester, J., Demidov, G. M., Demircioğlu, D., Dennis, N. M., Denroche, R. E., Dentro, S. C., Desai, N., Deshpande, V., Deshwar, A. G., Desmedt, C., Deu-Pons, J., Dhalla, N., Dhani, N. C., Dhingra, P., Dhir, R., DiBiase, A., Diamanti, K., Ding, L., Ding, S., Dinh, H. Q., Dirix, L., Doddapaneni, H., Donmez, N., Dow, M. T., Drapkin, R., Drechsel, O., Drews, R. M., Serge, S., Dudderidge, T., Dueso-Barroso, A., Dunford, A. J., Dunn, M., Dursi, L. J., Duthie, F. R., Dutton-Regester, K., Eagles, J., Easton, D. F., Edmonds, S., Edwards, P. A., Edwards, S. E., Eeles, R. 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G., Jacquemier, J., Jakrot, V., Jamieson, N. B., Jang, G. H., Jang, S. J., Jayaseelan, J. C., Jayasinghe, R., Jefferys, S. R., Jegalian, K., Jennings, J. L., Jeon, S.-H., Jerman, L., Ji, Y., Jiao, W., Johansson, P. A., Johns, A. L., Johns, J., Johnson, R., Johnson, T. A., Jolly, C., Joly, Y., Jonasson, J. G., Jones, C. D., Jones, D. R., Jones, D. T. W., Jones, N., Jones, S. J. M., Jonkers, J., Ju, Y. S., Juhl, H., Jung, J., Juul, M., Juul, R. I., Juul, S., Jäger, N., Kabbe, R., Kahles, A., Kahraman, A., Kaiser, V. B., Kakavand, H., Kalimuthu, S., von Kalle, C., Kang, K. J., Karaszi, K., Karlan, B., Karlić, R., Karsch, D., Kasaian, K., Kassahn, K. S., Katai, H., Kato, M., Katoh, H., Kawakami, Y., Kay, J. D., Kazakoff, S. H., Kazanov, M. D., Keays, M., Kebebew, E., Kefford, R. F., Kellis, M., Kench, J. G., Kennedy, C. J., Kerssemakers, J. N. A., Khoo, D., Khoo, V., Khuntikeo, N., Khurana, E., Kilpinen, H., Kim, H. K., Kim, H.-L., Kim, H.-Y., Kim, H., Kim, J., Kim, J., Kim, J. K., Kim, Y., King, T. A., Klapper, W., Kleinheinz, K., Klimczak, L. J., Knappskog, S., Kneba, M., Knoppers, B. M., Koh, Y., Komorowski, J., Komura, D., Komura, M., Kong, G., Kool, M., Korbel, J. O., Korchina, V., Korshunov, A., Koscher, M., Koster, R., Kote-Jarai, Z., Koures, A., Kovacevic, M., Kremeyer, B., Kretzmer, H., Kreuz, M., Krishnamurthy, S., Kube, D., Kumar, K., Kumar, P., Kumar, S., Kumar, Y., Kundra, R., Kübler, K., Küppers, R., Lagergren, J., Lai, P. H., Laird, P. W., Lakhani, S. R., Lalansingh, C. M., Lalonde, E., Lamaze, F. C., Lambert, A., Lander, E., Landgraf, P., Landoni, L., Langerød, A., Lanzós, A., Larsimont, D., Larsson, E., Lathrop, M., Lau, L. M. S., Lawerenz, C., Lawlor, R. T., Lawrence, M. S., Lazar, A. J., Lazic, A. M., Le, X., Lee, D., Lee, D., Lee, E. A., Lee, H. J., Lee, J. J.-K., Lee, J.-Y., Lee, J., Lee, M. T. M., Lee-Six, H., Lehmann, K.-V., Lehrach, H., Lenze, D., Leonard, C. R., Leongamornlert, D. A., Leshchiner, I., Letourneau, L., Letunic, I., Levine, D. A., Lewis, L., Ley, T., Li, C., Li, C. H., Li, H. I., Li, J., Li, L., Li, S., Li, S., Li, X., Li, X., Li, X., Li, Y., Liang, H., Liang, S.-B., Lichter, P., Lin, P., Lin, Z., Linehan, W. M., Lingjærde, O. C., Liu, D., Liu, E. M., Liu, F.-F. F., Liu, F., Liu, J., Liu, X., Livingstone, J., Livitz, D., Livni, N., Lochovsky, L., Loeffler, M., Long, G. V., Lopez-Guillermo, A., Lou, S., Louis, D. N., Lovat, L. B., Lu, Y., Lu, Y.-J., Lu, Y., Luchini, C., Lungu, I., Luo, X., Luxton, H. J., Lynch, A. G., Lype, L., López, C., López-Otín, C., Ma, E. Z., Ma, Y., MacGrogan, G., MacRae, S., Macintyre, G., Madsen, T., Maejima, K., Mafficini, A., Maglinte, D. T., Maitra, A., Majumder, P. P., Malcovati, L., Malikic, S., Malleo, G., Mann, G. J., Mantovani-Löffler, L., Marchal, K., Marchegiani, G., Mardis, E. R., Margolin, A. A., Marin, M. G., Markowetz, F., Markowski, J., Marks, J., Marques-Bonet, T., Marra, M. A., Marsden, L., Martens, J. W. 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M., Muñoz, A., Myers, J., Myklebost, O., Möller, P., Nagae, G., Nagrial, A. M., Nahal-Bose, H. K., Nakagama, H., Nakagawa, H., Nakamura, H., Nakamura, T., Nakano, K., Nandi, T., Nangalia, J., Nastic, M., Navarro, A., Navarro, F. C. P., Neal, D. E., Nettekoven, G., Newell, F., Newhouse, S. J., Newton, Y., Ng, A. W. T., Ng, A., Nicholson, J., Nicol, D., Nie, Y., Nielsen, G. P., Nielsen, M. M., Nik-Zainal, S., Noble, M. S., Nones, K., Northcott, P. A., Notta, F., O’Connor, B. D., O’Donnell, P., O’Donovan, M., O’Meara, S., O’Neill, B. P., O’Neill, J. R., Ocana, D., Ochoa, A., Oesper, L., Ogden, C., Ohdan, H., Ohi, K., Ohno-Machado, L., Oien, K. A., Ojesina, A. I., Ojima, H., Okusaka, T., Omberg, L., Ong, C. K., Ossowski, S., Ott, G., Ouellette, B. F. F., P’ng, C., Paczkowska, M., Paiella, S., Pairojkul, C., Pajic, M., Pan-Hammarström, Q., Papaemmanuil, E., Papatheodorou, I., Paramasivam, N., Park, J. W., Park, J.-W., Park, K., Park, K., Park, P. J., Parker, J. S., Parsons, S. L., Pass, H., Pasternack, D., Pastore, A., Patch, A.-M., Pauporté, I., Pea, A., Pearson, J. V., Pedamallu, C. S., Pedersen, J. S., Pederzoli, P., Peifer, M., Pennell, N. A., Perou, C. M., Perry, M. D., Petersen, G. M., Peto, M., Petrelli, N., Petryszak, R., Pfister, S. M., Phillips, M., Pich, O., Pickett, H. A., Pihl, T. D., Pillay, N., Pinder, S., Pinese, M., Pinho, A. V., Pitkänen, E., Pivot, X., Piñeiro-Yáñez, E., Planko, L., Plass, C., Polak, P., Pons, T., Popescu, I., Potapova, O., Prasad, A., Preston, S. R., Prinz, M., Pritchard, A. L., Prokopec, S. D., Provenzano, E., Puente, X. S., Puig, S., Puiggròs, M., Pulido-Tamayo, S., Pupo, G. M., Purdie, C. A., Quinn, M. C., Rabionet, R., Rader, J. S., Radlwimmer, B., Radovic, P., Raeder, B., Raine, K. M., Ramakrishna, M., Ramakrishnan, K., Ramalingam, S., Raphael, B. J., Rathmell, W. K., Rausch, T., Reifenberger, G., Reimand, J., Reis-Filho, J., Reuter, V., Reyes-Salazar, I., Reyna, M. A., Reynolds, S. M., Rheinbay, E., Riazalhosseini, Y., Richardson, A. L., Richter, J., Ringel, M., Ringnér, M., Rino, Y., Rippe, K., Roach, J., Roberts, L. R., Roberts, N. D., Roberts, S. A., Robertson, A. G., Robertson, A. J., Rodriguez, J. B., Rodriguez-Martin, B., Rodríguez-González, F. G., Roehrl, M. H. A., Rohde, M., Rokutan, H., Romieu, G., Rooman, I., Roques, T., Rosebrock, D., Rosenberg, M., Rosenstiel, P. C., Rosenwald, A., Rowe, E. W., Royo, R., Rozen, S. G., Rubanova, Y., Rubin, M. A., Rubio-Perez, C., Rudneva, V. A., Rusev, B. C., Ruzzenente, A., Rätsch, G., Sabarinathan, R., Sabelnykova, V. Y., Sadeghi, S., Sahinalp, S. C., Saini, N., Saito-Adachi, M., Saksena, G., Salcedo, A., Salgado, R., Salichos, L., Sallari, R., Saller, C., Salvia, R., Sam, M., Samra, J. S., Sanchez-Vega, F., Sander, C., Sanders, G., Sarin, R., Sarrafi, I., Sasaki-Oku, A., Sauer, T., Sauter, G., Saw, R. P. M., Scardoni, M., Scarlett, C. J., Scarpa, A., Scelo, G., Schadendorf, D., Schein, J. E., Schilhabel, M. B., Schlesner, M., Schlomm, T., Schmidt, H. K., Schramm, S.-J., Schreiber, S., Schultz, N., Schumacher, S. E., Schwarz, R. F., Scolyer, R. A., Scott, D., Scully, R., Seethala, R., Segre, A. V., Selander, I., Semple, C. A., Senbabaoglu, Y., Sengupta, S., Sereni, E., Serra, S., Sgroi, D. C., Shackleton, M., Shah, N. C., Shahabi, S., Shang, C. A., Shang, P., Shapira, O., Shelton, T., Shen, C., Shen, H., Shepherd, R., Shi, R., Shi, Y., Shiah, Y.-J., Shibata, T., Shih, J., Shimizu, E., Shimizu, K., Shin, S. J., Shiraishi, Y., Shmaya, T., Shmulevich, I., Shorser, S. I., Short, C., Shrestha, R., Shringarpure, S. S., Shriver, C., Shuai, S., Sidiropoulos, N., Siebert, R., Sieuwerts, A. M., Sieverling, L., Signoretti, S., Sikora, K. O., Simbolo, M., Simon, R., Simons, J. V., Simpson, J. T., Simpson, P. T., Singer, S., Sinnott-Armstrong, N., Sipahimalani, P., Skelly, T. J., Smid, M., Smith, J., Smith-McCune, K., Socci, N. D., Sofia, H. J., Soloway, M. G., Song, L., Sood, A. K., Sothi, S., Sotiriou, C., Soulette, C. M., Span, P. N., Spellman, P. T., Sperandio, N., Spillane, A. J., Spiro, O., Spring, J., Staaf, J., Stadler, P. F., Staib, P., Stark, S. G., Stebbings, L., Stefánsson, Ó. A., Stegle, O., Stein, L. D., Stenhouse, A., Stewart, C., Stilgenbauer, S., Stobbe, M. D., Stratton, M. R., Stretch, J. R., Struck, A. J., Stuart, J. M., Stunnenberg, H. G., Su, H., Su, X., Sun, R. X., Sungalee, S., Susak, H., Suzuki, A., Sweep, F., Szczepanowski, M., Sültmann, H., Yugawa, T., Tam, A., Tamborero, D., Tan, B. K. T., Tan, D., Tan, P., Tanaka, H., Taniguchi, H., Tanskanen, T. J., Tarabichi, M., Tarnuzzer, R., Tarpey, P., Taschuk, M. L., Tatsuno, K., Tavaré, S., Taylor, D. F., Taylor-Weiner, A., Teague, J. W., Teh, B. T., Tembe, V., Temes, J., Thai, K., Thayer, S. P., Thiessen, N., Thomas, G., Thomas, S., Thompson, A., Thompson, A. M., Thompson, J. F. F., Thompson, R. H., Thorne, H., Thorne, L. B., Thorogood, A., Tiao, G., Tijanic, N., Timms, L. E., Tirabosco, R., Tojo, M., Tommasi, S., Toon, C. W., Toprak, U. H., Torrents, D., Tortora, G., Tost, J., Totoki, Y., Townend, D., Traficante, N., Treilleux, I., Trotta, J.-R., Trümper, L. H. P., Tsao, M., Tsunoda, T., Tubio, J. M. C., Tucker, O., Turkington, R., Turner, D. J., Tutt, A., Ueno, M., Ueno, N. T., Umbricht, C., Umer, H. M., Underwood, T. J., Urban, L., Urushidate, T., Ushiku, T., Uusküla-Reimand, L., Valencia, A., Van Den Berg, D. J., Van Laere, S., Van Loo, P., Van Meir, E. G., Van den Eynden, G. G., Van der Kwast, T., Vasudev, N., Vazquez, M., Vedururu, R., Veluvolu, U., Vembu, S., Verbeke, L. P. C., Vermeulen, P., Verrill, C., Viari, A., Vicente, D., Vicentini, C., VijayRaghavan, K., Viksna, J., Vilain, R. E., Villasante, I., Vincent-Salomon, A., Visakorpi, T., Voet, D., Vyas, P., Vázquez-García, I., Waddell, N. M., Waddell, N., Wadelius, C., Wadi, L., Wagener, R., Wala, J. A., Wang, J., Wang, J., Wang, L., Wang, Q., Wang, W., Wang, Y., Wang, Z., Waring, P. M., Warnatz, H.-J., Warrell, J., Warren, A. Y., Waszak, S. M., Wedge, D. C., Weichenhan, D., Weinberger, P., Weinstein, J. N., Weischenfeldt, J., Weisenberger, D. J., Welch, I., Wendl, M. C., Werner, J., Whalley, J. P., Wheeler, D. A., Whitaker, H. C., Wigle, D., Wilkerson, M. D., Williams, A., Wilmott, J. S., Wilson, G. W., Wilson, J. M., Wilson, R. K., Winterhoff, B., Wintersinger, J. A., Wiznerowicz, M., Wolf, S., Wong, B. H., Wong, T., Wong, W., Woo, Y., Wood, S., Wouters, B. G., Wright, A. J., Wright, D. W., Wright, M. H., Wu, C.-L., Wu, D.-Y., Wu, G., Wu, J., Wu, K., Wu, Y., Wu, Z., Xi, L., Xia, T., Xiang, Q., Xiao, X., Xing, R., Xiong, H., Xu, Q., Xu, Y., Xue, H., Yachida, S., Yakneen, S., Yamaguchi, R., Yamaguchi, T. N., Yamamoto, M., Yamamoto, S., Yamaue, H., Yang, F., Yang, H., Yang, J. Y., Yang, L., Yang, L., Yang, S., Yang, T.-P., Yang, Y., Yao, X., Yaspo, M.-L., Yates, L., Yau, C., Ye, C., Ye, K., Yellapantula, V. D., Yoon, C. J., Yoon, S.-S., Yousif, F., Yu, J., Yu, K., Yu, W., Yu, Y., Yuan, K., Yuan, Y., Yuen, D., Yung, C. K., Zaikova, O., Zamora, J., Zapatka, M., Zenklusen, J. C., Zenz, T., Zeps, N., Zhang, C.-Z., Zhang, F., Zhang, H., Zhang, H., Zhang, H., Zhang, J., Zhang, J., Zhang, J., Zhang, X., Zhang, X., Zhang, Y., Zhang, Z., Zhao, Z., Zheng, L., Zheng, X., Zhou, W., Zhou, Y., Zhu, B., Zhu, H., Zhu, J., Zhu, S., Zou, L., Zou, X., deFazio, A., van As, N., van Deurzen, C. H. M., van de Vijver, M. J., van’t Veer, L., & von Mering, C.
Affiliations
  • University of California San Diego (US)
  • Memorial Sloan Kettering Cancer Center (US)
  • Wellcome Sanger Institute (GB)
  • University of Chicago (US)
  • Gachon University (KR)
  • Hiroshima University (JP)
  • The University of Texas MD Anderson Cancer Center (US)
  • Ontario Institute for Cancer Research (CA)
  • BC Cancer Agency (CA)
  • The University of Melbourne (AU)
  • Universität Ulm (DE)
  • University of Verona (IT)
  • Oregon Health & Science University (US)
  • Washington University in St. Louis (US)
  • Deutsches Zentrum für Luft- und Raumfahrt e. V. (DLR) (DE)
  • Los Alamos National Laboratory (US)
  • University Health Network (CA)
  • German Cancer Research Center (DE)
  • Oslo University Hospital (NO)
  • University of Cambridge (GB)
  • University of Toronto (CA)
  • University of North Carolina at Chapel Hill (US)
  • Broad Institute (US)
  • University of Leeds (GB)
  • The University of Queensland (AU)
  • European Bioinformatics Institute (GB)
  • Johns Hopkins University (US)
  • Royal Stoke University Hospital (GB)
  • Chinese Academy of Sciences (CN)
  • La Trobe University (AU)
  • Buck Institute for Research on Aging (US)
  • Cedars-Sinai Medical Center (US)
  • University of Southern California (US)
  • Garvan Institute of Medical Research (AU)
  • Massachusetts General Hospital (US)
  • Friedrich-Ebert-Krankenhaus (DE)
  • Barcelona Supercomputing Center (ES)
  • Yale University (US)
  • Universitat Pompeu Fabra (ES)
  • Tampere University (FI)
  • Fox Chase Cancer Center (US)
  • Radboud University Nijmegen (NL)
  • University of East Anglia (GB)
  • Brigham and Women's Hospital (US)
  • University of Copenhagen (DK)
  • The University of Sydney (AU)
  • University of California, San Francisco (US)
  • Royal Marsden NHS Foundation Trust (GB)
  • Institute of Cancer Research (GB)
  • Institut Gustave Roussy (FR)
  • University of Bern (CH)
  • University of Pavia (IT)
  • University of Alabama at Birmingham (US)
  • University of Tasmania (AU)
  • National Institutes of Health (US)
  • Mayo Clinic (US)
  • Electronics and Telecommunications Research Institute (KR)
  • Korea Advanced Institute of Science and Technology (KR)
  • National Cancer Centre Singapore (SG)
  • University of Auckland (NZ)
  • Royal Children's Hospital (AU)
  • Vancouver Prostate Centre (CA)
  • Mount Sinai Hospital (CA)
  • Harvard University (US)
  • Baylor College of Medicine (US)
  • University of Cologne (DE)
  • Barking, Havering And Redbridge University Hospitals NHS Trust (GB)
  • University of Geneva (CH)
  • The Francis Crick Institute (GB)
  • Institut Jules Bordet (BE)
  • Princess Margaret Cancer Centre (CA)
  • Weill Cornell Medicine (US)
  • Uppsala University (SE)
  • University of Antwerp (BE)
  • Simon Fraser University (CA)
  • Universitat de Vic - Universitat Central de Catalunya (ES)
  • University of Glasgow (GB)
  • Barcelona Institute of Science and Technology (ES)
  • Icelandic Cancer Society (IS)
  • University of Padua (IT)
  • Australian Institute of Tropical Health and Medicine (AU)
  • Bioplatforms Australia (AU)
  • Erasmus MC (NL)
  • Institute for Research in Biomedicine (ES)
  • BGI Group (China) (CN)
  • University of California, Santa Cruz (US)
  • University of Miami (US)
  • St Thomas' Hospital (GB)
  • Lund University (SE)
  • Leibniz Institute of Virology (LIV) (DE)
  • Aarhus University (DK)
  • Government of India (IN)
  • Christian-Albrechts-Universität zu Kiel (DE)
  • University of British Columbia (CA)
  • University of Oxford (GB)
  • Stanford Medicine (US)
  • Goethe University Frankfurt (DE)
  • UC San Diego Health System (US)
  • Howard Hughes Medical Institute (US)
  • Salford Royal NHS Foundation Trust (GB)
  • Peking University (CN)
  • Children's Hospital of Philadelphia (US)
  • Hallym University (KR)
  • Aarhus University Hospital (DK)
  • Amsterdam UMC Location University of Amsterdam (NL)
  • Hong Kong University of Science and Technology (HK)
  • Duke-NUS Medical School (SG)
  • Charité – Universitätsmedizin Berlin (DE)
  • Edinburgh Royal Infirmary (GB)
  • Max Delbrück Center (DE)
  • Institute of Medical Science, The University of Tokyo (JP)
  • Michael E. DeBakey VA Medical Center (US)
  • European Molecular Biology Laboratory (DE)
  • University of Ljubljana (SI)
  • Endeavor Health (US)
  • RIKEN Center for Integrative Medical Sciences (JP)
  • Hopp Children's Cancer Center Heidelberg (DE)
  • Cancer Research UK (GB)
  • The Netherlands Cancer Institute (NL)
  • Oxford Nanopore Technologies (United Kingdom) (GB)
  • SIB Swiss Institute of Bioinformatics (CH)
  • University of Zagreb (HR)
  • University Hospital Schleswig-Holstein (DE)
  • South Australia Pathology (AU)
  • National Cancer Center Research Institute (JP)
  • Ewha Womans University (KR)
  • University College London (GB)
  • McGill University and Génome Québec Innovation Centre (CA)
  • Seoul National University (KR)
  • Seven Bridges Genomics (United States) (US)
  • University of Göttingen (DE)
  • Van Andel Institute (US)
  • Children's Medical Research Institute (AU)
  • Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
  • Boston Children's Hospital (US)
  • Institute of Biomedical Sciences, Academia Sinica (TW)
  • University of Oslo (NO)
  • Queen Mary University of London (GB)
  • Universidad de Oviedo (ES)
  • National Institute of Biomedical Genomics (IN)
  • Australian National University (AU)
  • Duke University (US)
  • Institució Catalana de Recerca i Estudis Avançats (ES)
  • Heidelberg Academy of Sciences and Humanities (DE)
  • Penrose-St. Francis Health Services (US)
  • Research Center for Advanced Science and Technology, The University of Tokyo (JP)
  • Hokkaido University (JP)
  • National Cancer Centre Japan (JP)
  • St. Jude Children's Research Hospital (US)
  • Carleton College (US)
  • Sage Bionetworks (US)
  • Keio University (JP)
  • Nottingham University Hospitals NHS Trust (GB)
  • Cleveland Clinic (US)
  • Christiana Care Health System (US)
  • SRA International (United States) (US)
  • Guy's Hospital (GB)
  • Spanish National Cancer Research Centre (ES)
  • German Cancer Aid (DE)
  • Inserm (FR)
  • Royal Surrey County Hospital (GB)
  • Medical College of Wisconsin (US)
  • Princeton University (US)
  • Vanderbilt University (US)
  • Institute for Systems Biology (US)
  • The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (US)
  • Institut Regional du Cancer de Montpellier (FR)
  • Norfolk and Norwich University Hospital (GB)
  • University of Würzburg (DE)
  • North Bristol NHS Trust (GB)
  • GZA Ziekenhuizen Campus Sint-Augustinus (BE)
  • University of Pittsburgh (US)
  • International Genomics Consortium (US)
  • Japan Agency for Medical Research and Development (JP)
  • Korea University (KR)
  • Walter Reed National Military Medical Center (US)
  • University Hospitals Coventry and Warwickshire NHS Trust (GB)
  • University of Iceland (IS)
  • National Center for Tumor Diseases (DE)
  • Singapore General Hospital (SG)
  • University of Helsinki (FI)
  • Universidade de Santiago de Compostela (ES)
  • Ninewells Hospital (GB)
  • Heidelberg University (DE)
  • Maastricht University (NL)
  • Lyon 1 Université (FR)
  • University Hospitals Birmingham NHS Foundation Trust (GB)
  • Tokyo Medical and Dental University (JP)
  • Queen's University Belfast (GB)
  • Tallinn University of Technology (EE)
  • QIMR Berghofer Medical Research Institute (AU)
  • Augusta University (US)
  • Centre for Human Genetics (GB)
  • Nationwide Children's Hospital (US)
  • Poznan University of Medical Sciences (PL)
  • MRC University of Glasgow Centre for Virus Research (GB)
  • Peking University Cancer Hospital (CN)
  • Hefei University of Technology (CN)
  • Chinese University of Hong Kong (HK)
  • Northwestern University (US)
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2020-02-05
Volume
578
Issue
7793
Pages
94-101
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/s41586-020-1943-3
PMC
PMC7054213
OpenAlex
W3004480399
Cited by
3,496
References
66
Citations by year
2026: 416 · 2025: 515 · 2024: 534 · 2023: 660 · 2022: 561 · 2021: 520 · 2020: 273 · 2019: 14 · 2018: 2 · 2014: 1
FWCI
174.85
Type
journal article
Language
en
Update notices
correction (2023-01-25)
Open access
Licence
Locations
  • Nature (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
  • Opin vísindi (Opin vísindi) (submittedVersion, cc-by-nc-sa)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • Työväentutkimus Vuosikirja (submittedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, cc-by)
  • Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
Funders
  • Massachusetts General Hospital
  • Wellcome Trust (103721/Z/14/Z, 206194)
  • Broad Institute
  • Duke-NUS Medical School
  • Cancer Research UK (23526, 29076, C98/A24032, 24032)
  • National Institutes of Health (C98/A24032)
  • Medical Research Council (C98/A24032)
  • National Medical Research Council (MOH-000032/MOH- CIRG18may-0004, NMRC/CIRG/1422/2015, CIRG/1422/2015)
  • National Cancer Institute (U24CA143843, U24CA143845, P30CA023100, U24CA210999, P01CA206978, P30CA016672)
  • National Institute of General Medical Sciences (T32GM008313, GM008313, NIGMS T32 GM008313)
  • National Institute of Environmental Health Sciences (ZIAES103266)
  • H2020 European Research Council (682398)
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
mutational signatures, somatic mutations, cancer genomics, mutational processes, DNA damage and repair, DNA replication, environmental exposure
MeSH terms
Age Factors, Base Sequence, Humans, Mutation, Neoplasms, Genome, Human, Sequence Analysis, DNA, Exome

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