A somatic-mutational process recurrently duplicates germline susceptibility loci and tissue-specific super-enhancers in breast cancers
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Somatic rearrangements contribute to the mutagenized landscape of cancer genomes. Here, we systematically interrogated rearrangements in 560 breast cancers by using a piecewise constant fitting approach. We identified 33 hotspots of large (>100 kb) tandem duplications, a mutational signature associated with homologous-recombination-repair deficiency. Notably, these tandem-duplication hotspots were enriched in breast cancer germline susceptibility loci (odds ratio (OR) = 4.28) and breast-specific 'super-enhancer' regulatory elements (OR = 3.54). These hotspots may be sites of selective susceptibility to double-strand-break damage due to high transcriptional activity or, through incrementally increasing copy number, may be sites of secondary selective pressure. The transcriptomic consequences ranged from strong individual oncogene effects to weak but quantifiable multigene expression effects. We thus present a somatic-rearrangement mutational process affecting coding sequences and noncoding regulatory elements and contributing a continuum of driver consequences, from modest to strong effects, thereby supporting a polygenic model of cancer development.
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The broadened intermediate category was enriched for hypermutators of rearrangement signature RS1, with RS1 predominant and exceeding 100 RS1 rearrangements.
“The intermediate category is also enriched for hypermutators of a rearrangement signature of long tandem-duplications (RS1) (where RS1 is predominant, exceeding 100 RS1 rearrangements)26.”
From Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study (2019) · cites this paper as [26]
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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-citationVelvet: 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 9,387 · see citing works
Self-citationWhole genomes redefine the mutational landscape of pancreatic cancer
Initiative, A. P. C. G., Waddell, N., Pajic, M., Patch, A.-M., Chang, D. K., Kassahn, K. S., Bailey, P., Johns, A. L., Miller, D., Nones, K., et al. (2015) · Nature · doi:10.1038/nature14169 · Cited by 2,642 · see citing works
Genome-wide association study identifies novel breast cancer susceptibility loci
Easton, D. F., Pooley, K. A., Dunning, A. M., Pharoah, P. D. P., Thompson, D., Ballinger, D. G., Struewing, J. P., Morrison, J., Field, H., Luben, R., et al. (2007) · Nature · doi:10.1038/nature05887 · Cited by 2,319 · 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-citationMutational Processes Molding the Genomes of 21 Breast Cancers
Nik-Zainal, S., Alexandrov, L. B., Wedge, D. C., Van Loo, P., Greenman, C. D., Raine, K., Jones, D., Hinton, J., Marshall, J., Stebbings, L. A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.024 · Cited by 1,909 · see citing works
Self-citationHighly Recurrent <i>TERT</i> Promoter Mutations in Human Melanoma
Huang, F. W., Hodis, E., Xu, M. J., Kryukov, G. V., Chin, L., & Garraway, L. A. (2013) · Science · doi:10.1126/science.1229259 · Cited by 1,816 · see citing works
Whole–genome characterization of chemoresistant ovarian cancer
Patch, A., Christie, E. L., Etemadmoghadam, D., Garsed, D. W., George, J., Fereday, S., Nones, K., Cowin, P. A., Alsop, K., Bailey, P. J., et al. (2015) · Nature · doi:10.1038/nature14410 · Cited by 1,551 · see citing works
Repair Pathway Choices and Consequences at the Double-Strand Break
Ceccaldi, R., Rondinelli, B., & D’Andrea, A. D. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.07.009 · Cited by 1,499 · see citing works
Activating ESR1 mutations in hormone-resistant metastatic breast cancer
Robinson, D. R., Wu, Y.-M., Vats, P., Su, F., Lonigro, R. J., Cao, X., Kalyana-Sundaram, S., Wang, R., Ning, Y., Hodges, L., et al. (2013) · Nature Genetics · doi:10.1038/ng.2823 · Cited by 1,145 · see citing works
Frequency of TERT promoter mutations in human cancers
Vinagre, J., Almeida, A., Pópulo, H., Batista, R., Lyra, J., Pinto, V., Coelho, R., Celestino, R., Prazeres, H., Lima, L., et al. (2013) · Nature Communications · doi:10.1038/ncomms3185 · Cited by 898 · see citing works
Mechanisms underlying mutational signatures in human cancers
Helleday, T., Eshtad, S., & Nik‐Zainal, S. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3729 · Cited by 841 · see citing works
Self-citationComplex landscapes of somatic rearrangement in human breast cancer genomes
Stephens, P. J., McBride, D. J., Lin, M., Varela, I., Pleasance, E., Simpson, J. T., Stebbings, L. A., Leroy, C., Edkins, S., Mudie, L. J., et al. (2009) · Nature · doi:10.1038/nature08645 · Cited by 833 · see citing works
Self-citationModelling Myc inhibition as a cancer therapy
Soucek, L., Whitfield, J. R., Martins, C. P., Finch, A. J., Murphy, D. J., Sodir, N. M., Karnezis, A. N., Swigart, L. B., Nasi, S., & Evan, G. I. (2008) · Nature · doi:10.1038/nature07260 · Cited by 822 · see citing works
Self-citationNon-coding recurrent mutations in chronic lymphocytic leukaemia
Puente, X. S., Beà, S., Valdés‐Mas, R., Villamor, N., Gutiérrez‐Abril, J., Martín-Subero, J. I., Munar, M., Rubio-Pérez, C., Jares, P., Aymerich, M., et al. (2015) · Nature · doi:10.1038/nature14666 · Cited by 813 · see citing works
Self-citationSources of DNA Double-Strand Breaks and Models of Recombinational DNA RepairPreprint
Mehta, A., & Haber, J. E. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016428 · Cited by 727 · see citing works
Genome-wide association study identifies five new breast cancer susceptibility loci
The Breast Cancer Susceptibility Collaboration (UK), Turnbull, C., Ahmed, S., Morrison, J., Pernet, D., Renwick, A., Maranian, M., Seal, S., Ghoussaini, M., Hines, S., et al. (2010) · Nature Genetics · doi:10.1038/ng.586 · Cited by 687 · see citing works
Self-citationLi, S., Shen, D., Shao, J., Crowder, R. J., Liu, W., Prat, A., He, X., Liu, S., Hoog, J., Lu, C., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.08.022 · Cited by 623 · see citing works
A common coding variant in CASP8 is associated with breast cancer risk
Cox, A., Dunning, A. M., García‐Closas, M., Balasubramanian, S. P., Reed, M., Pooley, K. A., Scollen, S., Baynes, C., Ponder, B. A. J., Chanock, S. J., et al. (2007) · Nature Genetics · doi:10.1038/ng1981 · Cited by 610 · see citing works
Self-citationBOCS, Michailidou, K., kConFab Investigators, AOCS Group, NBCS, GENICA Network, Beesley, J., Lindström, S., Canisius, S., Dennis, J., et al. (2015) · Nature Genetics · doi:10.1038/ng.3242 · Cited by 593 · see citing works
ENCODE data at the ENCODE portal
Sloan, C. A., Chan, E. T., Davidson, J. M., Malladi, V. S., Strattan, J. S., Hitz, B. C., Gabdank, I., Narayanan, A. K., Ho, M., Lee, B. T., et al. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv1160 · Cited by 549 · see citing works
Non-coding recurrent mutations in chronic lymphocytic leukaemia
Puente, X. S., Beà, S., Valdés‐Mas, R., Villamor, N., Gutiérrez‐Abril, J., Martín-Subero, J. I., Munar, M., Rubio-Pérez, C., Jares, P., Aymerich, M., et al. (2016) · Nature · doi:10.1038/nature18910 · Cited by 546 · see citing works
Thomas, G. D., Jacobs, K. B., Kraft, P., Yeager, M., Wacholder, S., Cox, D. G., Hankinson, S. E., Hutchinson, A. A., Wang, Z., Yu, K. F., et al. (2009) · Nature Genetics · doi:10.1038/ng.353 · Cited by 536 · see citing works
Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2
SEARCH, Ahmed, S., kConFab, Australian Ovarian Cancer Study Group, Thomas, G. D., Ghoussaini, M., Healey, C. S., Humphreys, M. K., Platte, R., Morrison, J., et al. (2009) · Nature Genetics · doi:10.1038/ng.354 · Cited by 477 · see citing works
Self-citationRole of SWI/SNF in acute leukemia maintenance and enhancer-mediated <i>Myc</i> regulation
Shi, J., Whyte, W. A., Zepeda-Mendoza, C. J., Milazzo, J. P., Shen, C., Roe, J.-S., Minder, J. L., Mercan, F., Wang, E., Eckersley-Maslin, M. A., et al. (2013) · Genes & Development · doi:10.1101/gad.232710.113 · Cited by 463 · see citing works
Common variants on chromosome 5p12 confer susceptibility to estrogen receptor–positive breast cancer
Stacey, S., Manolescu, A. R., Sulem, P., Thorlacius, S., Gudjonsson, S. A., Jónsson, G. F., Jakobsdottir, M., Bergþorsson, J. Þ., Guðmundsson, J., Aben, K. K. H., et al. (2008) · Nature Genetics · doi:10.1038/ng.131 · Cited by 459 · see citing works
Easton, D. F., Deffenbaugh, A. M., Pruss, D., Frye, C., Wenstrup, R. J., Allen-Brady, K., Tavtigian, S. V., Monteiro, A. N. A., Iversen, E. S., Couch, F. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/521032 · Cited by 455 · see citing works
Self-citationBreak-Induced Replication Repair of Damaged Forks Induces Genomic Duplications in Human Cells
Costantino, L., Sotiriou, S. K., Rantala, J., Magin, S., Mladenov, E., Helleday, T., Haber, J. E., Iliakis, G. E., Kallioniemi, O., & Halazonetis, T. D. (2013) · Science · doi:10.1126/science.1243211 · Cited by 451 · see citing works
Zerbino, D. R., Wilder, S. P., Johnson, N., Juettemann, T., & Flicek, P. R. (2015) · Genome Biology · doi:10.1186/s13059-015-0621-5 · Cited by 429 · see citing works
Genome-wide association studies identify four ER negative–specific breast cancer risk loci
The Gene ENvironmental Interaction and breast CAncer (GENICA) Network, García‐Closas, M., kConFab Investigators, (FBCS), F. B. C. S., Australian Breast Cancer Tissue Bank (ABCTB) Investigators, Couch, F. J., Lindström, S., Michailidou, K., Schmidt, M. K., Brook, M. N., et al. (2013) · Nature Genetics · doi:10.1038/ng.2561 · Cited by 406 · see citing works
Identification of focally amplified lineage-specific super-enhancers in human epithelial cancers
Zhang, X., Choi, P. S., Francis, J. M., Imielinski, M. B., Watanabe, H., Cherniack, A. D., & Meyerson, M. M. (2015) · Nature Genetics · doi:10.1038/ng.3470 · Cited by 341 · see citing works
Migrating bubble during break-induced replication drives conservative DNA synthesis
Saini, N., Ramakrishnan, S., Elango, R., Ayyar, S., Zhang, Y., Deem, A. K., Ira, G., Haber, J. E., Lobachev, K. S., & Malkova, A. (2013) · Nature · doi:10.1038/nature12584 · Cited by 326 · see citing works
Copynumber: Efficient algorithms for single- and multi-track copy number segmentation
Nilsen, G., Liestøl, K., Loo, P. V., Vollan, H. K. M., Brodtkorb, M., Rueda, O. M., Chin, S., Russell, R., Baumbusch, L. O., Caldas, C., et al. (2012) · BMC Genomics · doi:10.1186/1471-2164-13-591 · Cited by 302 · see citing works
Self-citationThe topography of mutational processes in breast cancer genomes
Morganella, S., Alexandrov, L. B., Głodzik, D., Zou, X., Davies, H. R., Staaf, J., Sieuwerts, A. M., Brinkman, A. B., Martin, S., Ramakrishna, M., et al. (2016) · Nature Communications · doi:10.1038/ncomms11383 · Cited by 252 · see citing works
Self-citationSiddiq, A., Couch, F. J., Chen, G. K., Lindström, S., Eccles, D., Millikan, R. C., Michailidou, K., Stram, D. O., Beckmann, L., Rhie, S. K., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds381 · Cited by 176 · see citing works
Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidney
Roy, A., Kumar, V., Zorman, B., Fang, E., Haines, K. M., Doddapaneni, H., Hampton, O. A., White, S. J., Bavle, A. A., Patel, N. R., et al. (2015) · Nature Communications · doi:10.1038/ncomms9891 · Cited by 161 · see citing works
The 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
The tandem duplicator phenotype as a distinct genomic configuration in cancer
Menghi, F., Inaki, K., Woo, X., Kumar, P., Grzȩda, K. R., Malhotra, A., Yadav, V. K., Kim, H., Márquez, E. J., Ucar, D., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1520010113 · Cited by 115 · see citing works
Wei, Y., Zhang, S., Shang, S., Zhang, B., Li, S., Wang, X., Wang, F., Su, J., Wu, Q., Liu, H., et al. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv1243 · Cited by 104 · see citing works
Tandem duplication of chromosomal segments is common in ovarian and breast cancer genomes
McBride, D. J., Etemadmoghadam, D., Cooke, S. L., Alsop, K., George, J., Butler, A. P., Cho, J., Galappaththige, D., Greenman, C., Howarth, K., et al. (2012) · The Journal of Pathology · doi:10.1002/path.4042 · Cited by 97 · see citing works
Self-citationDeciphering the Code of the Cancer Genome: Mechanisms of Chromosome Rearrangement
Willis, N. A., Rass, E., & Scully, R. (2015) · Trends in cancer · doi:10.1016/j.trecan.2015.10.007 · Cited by 62 · see citing works
Nilsson, B., Johansson, M., Heyden, A., Nelander, S., & Fioretos, T. (2008) · Genome biology · doi:10.1186/gb-2008-9-1-r13 · Cited by 23 · see citing works
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Aung, K. L., Fischer, S. E., Denroche, R. E., Jang, G.-H., Dodd, A., Creighton, S., Southwood, B., Liang, S.-B., Chadwick, D., Zhang, A., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-2994 · Cited by 618 · see citing works
Chromothripsis drives the evolution of gene amplification in cancer
Shoshani, O., Brunner, S. F., Yaeger, R. D., Ly, P., Nechemia‐Arbely, Y., Kim, D. H., Fang, R., Castillon, G. A., Yu, M., Li, J. S. Z., et al. (2020) · Nature · doi:10.1038/s41586-020-03064-z · Cited by 474 · see citing works
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Cho, S. W., Xu, J., Sun, R., Mumbach, M. R., Carter, A. C., Chen, Y. G., Yost, K. E., Kim, J., He, J., Nevins, S. A., et al. (2018) · Cell · doi:10.1016/j.cell.2018.03.068 · Cited by 459 · see citing works
Genome-wide association studies of cancer: current insights and future perspectives
Sud, A., Kinnersley, B., & Houlston, R. S. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2017.82 · Cited by 383 · see citing works
Viswanathan, S. R., Ha, G., Hoff, A. M., Wala, J. A., Carrot-Zhang, J., Whelan, C. W., Haradhvala, N. J., Freeman, S. S., Reed, S. C., Rhoades, J., et al. (2018) · Cell · doi:10.1016/j.cell.2018.05.036 · Cited by 365 · see citing works
Degasperi, A., Amarante, T. D., Czarnecki, J., Shooter, S., Zou, X., Glodzik, D., Morganella, S., Nanda, A. S., Badja, C., Koh, G., et al. (2020) · Nature Cancer · doi:10.1038/s43018-020-0027-5 · Cited by 304 · see citing works
Self-citationWhole-genome sequencing of triple-negative breast cancers in a population-based clinical study
Staaf, J., Glodzik, D., Bosch, A., Vallon-Christersson, J., Reuterswärd, C., Häkkinen, J., Degasperi, A., Amarante, T. D., Saal, L. H., Hegardt, C., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0582-4 · Cited by 307 · see citing works
Self-citationLetouzé, É., Shinde, J., Renault, V., Couchy, G., Blanc, J., Tubacher, E., Bayard, Q., Bacq, D., Meyer, V., Semhoun, J., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01358-x · Cited by 290 · see citing works
Mutational signatures: emerging concepts, caveats and clinical applications
Koh, C. C., Degasperi, A., Zou, X., Momen, S., & Nik‐Zainal, S. (2021) · Nature reviews. Cancer · doi:10.1038/s41568-021-00377-7 · Cited by 276 · see citing works
Self-citationCaswell, D. R., & Swanton, C. (2017) · BMC Medicine · doi:10.1186/s12916-017-0900-y · Cited by 219 · see citing works
The genomic landscape of 2,023 colorectal cancers
Cornish, A. J., Gruber, A. J., Kinnersley, B., Chubb, D., Frangou, A., Caravagna, G., Noyvert, B., Lakatos, E., Wood, H. M., Thorn, S., et al. (2024) · Nature · doi:10.1038/s41586-024-07747-9 · Cited by 194 · see citing works
Self-citationMenghi, F., Barthel, F. P., Yadav, V. K., Tang, M., Ji, B., Tang, Z., Carter, G. W., Ruan, Y., Scully, R., Verhaak, R. G. W., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.06.008 · Cited by 169 · see citing works
Thandapani, P. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.02.014 · Cited by 163 · see citing works
BET Family Protein BRD4: An Emerging Actor in NFκB Signaling in Inflammation and Cancer
Hajmirza, A., Emadali, A., Gauthier, A., Casasnovas, O., Gressin, R., & Callanan, M. B. (2018) · Biomedicines · doi:10.3390/biomedicines6010016 · Cited by 159 · see citing works
Bayard, Q., Meunier, L., Péneau, C., Renault, V., Shinde, J., Nault, J., Mami, I., Couchy, G., Amaddeo, G., Tubacher, E., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-07552-9 · Cited by 156 · see citing works
Validating the concept of mutational signatures with isogenic cell models
Zou, X., Owusu, M., Harris, R., Jackson, S. P., Loizou, J. I., & Nik‐Zainal, S. (2018) · Nature Communications · doi:10.1038/s41467-018-04052-8 · Cited by 142 · see citing works
Self-citationGuo, Y. A., Chang, M. M., Huang, W., Ooi, W. F., Xing, M., Tan, P. B. O., & Skanderup, A. J. (2018) · Nature Communications · doi:10.1038/s41467-018-03828-2 · Cited by 149 · see citing works
Mutational Signatures in Breast Cancer: The Problem at the DNA Level
Nik‐Zainal, S., & Morganella, S. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-2810 · Cited by 132 · see citing works
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Steele, C. D., Tarabichi, M., Oukrif, D., Webster, A. P., Ye, H., Fittall, M. W., Lombard, P., Martincorena, I., Tarpey, P. S., Collord, G., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.02.002 · Cited by 132 · see citing works
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Rustad, E. H., Yellapantula, V. D., Głodzik, D., Maclachlan, K. H., Diamond, B. T., Boyle, E. M., Ashby, C., Blaney, P., Gundem, G., Hultcrantz, M. L., et al. (2020) · Blood Cancer Discovery · doi:10.1158/2643-3230.bcd-20-0132 · Cited by 120 · see citing works
Self-citationComputational analysis of cancer genome sequencing data
Cortés‐Ciriano, I., Gulhan, D., Lee, J. J.-K., Melloni, G. E. M., & Park, P. J. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-021-00431-y · Cited by 116 · see citing works
Wang, C., Yin, R. H., Dai, J., Gu, Y., Cui, S., Ma, H., Zhang, Z., Huang, J., Qin, N., Jiang, T., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04492-2 · Cited by 115 · see citing works
Patterns and mechanisms of structural variations in human cancer
Yi, K., & Ju, Y. S. (2018) · Experimental & Molecular Medicine · doi:10.1038/s12276-018-0112-3 · Cited by 101 · see citing works
Xing, R., Zhou, Y., Yu, J., Yu, Y., Nie, Y., Luo, W., Yang, C., Xiong, T., Wu, W. K. K., Li, Z., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09644-6 · Cited by 85 · see citing works
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Zhang, J., Liu, W., Zou, C., Zhao, Z., Lai, Y., Shi, Z., Xie, X., Huang, G., Wang, Y., Zhang, X., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-1418 · Cited by 68 · see citing works
Deng, R., Huang, J.-H., Wang, Y., Zhou, L.-H., Wang, Z., Hu, B., Chen, Y., Yang, D., Mai, J., Li, Z., et al. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01236-z · Cited by 66 · see citing works
Gonçalves, E., Behan, F. M., Louzada, S., Arnol, D., Stronach, E. A., Yang, F., Yusa, K., Stegle, O., Iorio, F., & Garnett, M. J. (2019) · Genome biology · doi:10.1186/s13059-019-1637-z · Cited by 60 · see citing works
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O'Kane, G. M., Connor, A. A., & Gallinger, S. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.10.007 · Cited by 60 · see citing works
Menghi, F., Banda, K., Kumar, P., Straub, R., Dobrolecki, L. E., Rodriguez, I. V., Yost, S. E., Chandok, H., Radke, M. R., Zhu, A. S., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abn1926 · Cited by 58 · see citing works
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Zhang, T., Song, X., Zhang, Z., Mao, Q., Xia, W., Xu, L., Jiang, F., & Dong, G. (2020) · Oncogenesis · doi:10.1038/s41389-020-00277-9 · Cited by 39 · see citing works
Wu, C., & Pan, W. (2018) · Genetics · doi:10.1534/genetics.118.300805 · Cited by 37 · see citing works
Enhancer reprogramming in tumor progression: a new route towards cancer cell plasticity
Fagnocchi, L., Poli, V., & Zippo, A. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2820-1 · Cited by 35 · see citing works
Genomic Rearrangement Signatures and Clinical Outcomes in High-Grade Serous Ovarian Cancer
Hillman, R. T., Chisholm, G. B., Lu, K. H., & Futreal, P. A. (2017) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djx176 · Cited by 34 · see citing works
Genome-guided discovery of cancer therapeutic targets
Konda, P., Garinet, S., Allen, E. M. V., & Viswanathan, S. R. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112978 · Cited by 35 · see citing works
Translational Genomics: Practical Applications of the Genomic Revolution in Breast Cancer
Yates, L. R., & Desmedt, C. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-2548 · Cited by 31 · see citing works
Dysregulated Transcriptional Control in Prostate Cancer
Baumgart, S. J., Nevedomskaya, E., & Haendler, B. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20122883 · Cited by 30 · see citing works
Patterns of structural variation define prostate cancer across disease states
Zhou, M., Ko, M., Hoge, A. C. H., Luu, K., Liu, Y., Russell, M. L., Hannon, W. W., Zhang, Z., Carrot‐Zhang, J., Beroukhim, R., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.161370 · Cited by 27 · see citing works
Etiology of super-enhancer reprogramming and activation in cancer
Zhou, R. W., & Parsons, R. E. (2023) · Epigenetics & Chromatin · doi:10.1186/s13072-023-00502-w · Cited by 30 · see citing works
Visualizing and exploring patterns of large mutational events with SigProfilerMatrixGenerator
Khandekar, A., Vangara, R., Barnes, M. D., Díaz‐Gay, M., Abbasi, A., Bergstrom, E. N., Steele, C. D., Pillay, N., & Alexandrov, L. B. (2023) · BMC Genomics · doi:10.1186/s12864-023-09584-y · Cited by 26 · see citing works
Self-citationModeling double strand break susceptibility to interrogate structural variation in cancer
Ballinger, T. J., Bouwman, B. A. M., Mirzazadeh, R., Garnerone, S., Crosetto, N., & Semple, C. A. M. (2019) · Genome biology · doi:10.1186/s13059-019-1635-1 · Cited by 22 · see citing works
Mas-Ponte, D., McCullough, M., & Supek, F. (2022) · Clinical Science · doi:10.1042/cs20210682 · Cited by 23 · see citing works
Cui, H., Zhou, Y., Wang, F., Cheng, C., Zhang, W., Sun, R., Zhang, L., Bi, Y., Guo, M., Zhou, Y., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-33994-3 · Cited by 23 · see citing works
G enomic hotspots but few recurrent fusion genes in breast cancer
Fimereli, D., Fumagalli, D., Brown, D. N., Gacquer, D., Rothé, F., Salgado, R., Larsimont, D., Sotiriou, C. P., & Detours, V. (2018) · Genes Chromosomes and Cancer · doi:10.1002/gcc.22533 · Cited by 22 · see citing works
Unmet Needs in Clinical Research in Breast Cancer: Where Do We Need to Go?
Partridge, A. H., & Carey, L. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-2633 · Cited by 21 · see citing works
Genomic landscape of adult testicular germ cell tumours in the 100,000 Genomes Project
Leathlobhair, M. N., Frangou, A., Kinnersley, B., Cornish, A. J., Chubb, D., Lakatos, E., Arumugam, P., Gruber, A. J., Law, P., Tapinos, A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-53193-6 · Cited by 20 · see citing works
Liang, C., Niu, L., Xiao, Z., Zheng, C., Shen, Y., Shi, Y., & Han, X. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.117218 · Cited by 20 · see citing works
Yoo, K. H., Hennighausen, L. G., & Shin, H. Y. (2018) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-018-9417-z · Cited by 18 · see citing works
Evolution and genomic signatures of spontaneous somatic mutation in Drosophila intestinal stem cellsPreprint
Riddiford, N., Siudeja, K., van den Beek, M., Boumard, B., & Bardin, A. J. (2020) · bioRxiv · doi:10.1101/gr.268441.120 · Cited by 12 · see citing works
Ng, A. W. T., Contino, G., Killcoyne, S., Devonshire, G., Hsu, R., Abbas, S., Su, J., Redmond, A. M., Weaver, J. M. J., Eldridge, M., et al. (2022) · Communications Biology · doi:10.1038/s42003-022-03238-7 · Cited by 15 · see citing works
Culliford, R., Lawrence, S. E. D., Mills, C., Tippu, Z., Chubb, D., Cornish, A. J., Browning, L., Kinnersley, B., Bentham, R. B., Sud, A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49692-1 · Cited by 16 · see citing works
Genomic landscape of diffuse glioma revealed by whole genome sequencing
Kinnersley, B., Jung, J., Cornish, A. J., Chubb, D., Laxton, R. C., Frangou, A., Gruber, A. J., Sud, A., Caravagna, G., Sottoriva, A., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-59156-9 · Cited by 15 · see citing works
Benedetto, C. D., Oh, J., Choudhery, Z., Shi, W., Valdés, G., & Betancur, P. A. (2022) · BMC Cancer · doi:10.1186/s12885-022-10157-7 · Cited by 12 · see citing works
Nowinski, S., Santaolalla, A., O’Leary, B., Loda, M. F., Mirchandani, A., Emberton, M., Hemelrijck, M. V., & Grigoriadis, A. E. (2018) · Oncotarget · doi:10.18632/oncotarget.24400 · Cited by 10 · see citing works
kConFab Investigators, Li, J., Li, H., Makunin, I. V., Thompson, B. A., Tao, K., Young, E. L., Lopez, J., Camp, N. J., Tavtigian, S. V., et al. (2017) · Breast Cancer Research and Treatment · doi:10.1007/s10549-017-4469-0 · Cited by 9 · see citing works
Mechanisms of tandem duplication in the cancer genome
Scully, R., Głodzik, D., Menghi, F., Liu, E. T., & Zhang, C. (2024) · DNA repair · doi:10.1016/j.dnarep.2024.103802 · Cited by 8 · see citing works
Chojnacka, M., Diamond, B. T., Landgren, O., & Maura, F. (2022) · Seminars in Oncology · doi:10.1053/j.seminoncol.2022.01.006 · Cited by 8 · see citing works
Genetic determinants and absence of breast cancer in Xavante Indians in Sangradouro Reserve, Brazil
Zhou, Y., Russo, J., Rueff, J., Pires, M. A. M., & de Castro, G. B. (2023) · Scientific Reports · doi:10.1038/s41598-023-28461-y · Cited by 8 · see citing works
Super-enhancer landscape rewiring in cancer: The epigenetic control at distal sites
Giorgio, E. D., Benetti, R., Kerschbamer, E., Xodo, L. E., & Brancolini, C. (2023) · International review of cytology · doi:10.1016/bs.ircmb.2023.03.013 · Cited by 8 · see citing works
Sequence of events in prostate cancer
Cotter, K. A., & Rubin, M. A. (2018) · Nature · doi:10.1038/d41586-018-06029-5 · Cited by 7 · see citing works
Holistic cancer genome profiling for every patient
Nik‐Zainal, S., Memari, Y., & Davies, H. R. (2020) · Swiss Medical Weekly · doi:10.4414/smw.2020.20158 · Cited by 6 · see citing works
Self-citationAccurate identification of structural variations from cancer samples
Li, L., Hong, C., Xu, J., Chung, C., Leung, A. K.-Y., Boncan, D. A. T., Cheng, L., Lo, K. W., Lai, P. B. S., Wong, J., et al. (2023) · Briefings in Bioinformatics · doi:10.1093/bib/bbad520 · Cited by 6 · see citing works
Breaking point: the genesis and impact of structural variation in tumours
Ewing, A., & Semple, C. A. M. (2018) · F1000Research · doi:10.12688/f1000research.16079.1 · Cited by 6 · see citing works
Revealing the impact of recurrent and rare structural variants in multiple myelomaPreprint
Rustad, E. H., Yellapantula, V. D., Głodzik, D., Maclachlan, K. H., Diamond, B. T., Boyle, E. M., Ashby, C., Blaney, P., Gundem, G., Hultcrantz, M. L., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2019.12.18.881086 · Cited by 5 · see citing works
Self-citationXia, T., Yin, H., Zhu, Q., Zhang, K., Xie, H., Shan, Y., Zhang, S., Zhu, R., Li, K., Miao, M., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102146 · Cited by 3 · see citing works
Comprehensive multi-omics analysis of tandem duplicator phenotypes in non-small cell lung cancer
Li, J., Pan, X., Bi, Y., Huang, J., Peng, J., Bai, C., Hou, J., & Yang, C. (2025) · Frontiers in Medicine · doi:10.3389/fmed.2025.1556840 · Cited by 2 · see citing works
Undifferentiated Sarcomas Develop Through Distinct Evolutionary PathwaysPreprint
Steele, C. D., Tarabichi, M., Alexandrov, L. B., Oukrif, D., Ye, H., Fittall, M. W., Lombard, P., Martincorena, I., Tarpey, P. S., Collord, G., et al. (2018) · SSRN Electronic Journal · doi:10.2139/ssrn.3204559 · Cited by 2 · see citing works
Self-citationSuspène, R., Raymond, K. A., Guardado‐Calvo, P., Dairou, J., Bonhomme, F., Bonenfant, C., Guyétant, S., Lecomte, T., Pagès, J., & Vartanian, J. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.108117 · Cited by 1 · see citing works
Decoding genomic rearrangements for cancer driver discovery
Seo, E., Park, S., Park, I., & Bhin, J. (2025) · Molecules and Cells · doi:10.1016/j.mocell.2025.100272 · Cited by 1 · see citing works
Cellular plasticity of cancer: roles of biomolecular condensates and ecDNA
Sugimoto, Y., Zhang, Y., Kachi, T., Ogami, K., & Suzuki, H. I. (2026) · Japanese Journal of Clinical Oncology · doi:10.1093/jjco/hyag065 · Cited by 1 · see citing works
Aberrant replication licensing drives Copy Number Gains across speciesPreprint
Nathanailidou, P., Petropoulos, M., Maxouri, S., Kasselimi, E., Symeonidou, I.-E., Preza, O., Spiliopoulou-Sdougkou, I., Beneš, V., Taraviras, S. L., & Lygerou, Z. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.10.10.334516
Design and Implementation of Cancer Structural Variants Hotspot Detection and Annotation Software
Lv, X., Liu, S., & Jiang, S. (2021) · Lecture notes on data engineering and communications technologies · doi:10.1007/978-3-030-81007-8_67
Semple, C. A. M. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.733132730.793552752
Hereditary Breast Cancer and Pathogenic Germline Variants
Velaga, R., Toi, M., Kawaguchi‐Sakita, N., Benson, J. R., & Senda, N. (2023) · Springer eBooks · doi:10.1007/978-981-19-7630-8_3
Genomic landscape of diffuse glioma revealed by whole genome sequencingPreprint
Kinnersley, B., Jung, J., Cornish, A. J., Chubb, D., Laxton, R. C., Frangou, A., Gruber, A. J., Sud, A., Caravagna, G., Sottoriva, A., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-3470361/v1
TONSL suppresses polymerase theta-dependent tandem duplications through chromatin-guided repair
van Schendel, R., Romeijn, R. J., Kralemann, L. E. M., Hooykaas, P. J. J., & Tijsterman, M. (2026) · Nature Communications · doi:10.1038/s41467-026-70905-2
Bella, T. L. (2018) · theses.fr (ABES) · doi:10.70675/e88d9a08za929z4c0fzb8d9z9f01cd69ca39
Analyse de signatures transcriptomiques et épigénétiques des carcinomes hépatocellulaires
Meunier, L. (2020) · theses.fr (ABES) · doi:10.70675/d5e7c2e4zaff4z46eaza0fcza52f9c3d46f1
Replication fork directionality reveals how structural variants arise under replication stressPreprint
Głodzik, D., Rigby, M., Andreopoulos, M., Crawford, J., Ehmsen, S. R., Tapinos, A., Cornish, A., Houlston, R. S., Wedge, D. C., Scully, R., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.29.735381
Global signatures of Ribonucleotide Excision Repair deficiency and its therapeutic vulnerabilitiesPreprint
Toong, P. J., Boushaki, S., Zhao, S. J., Brough, R., Song, F., Krastev, D. B., Black, D., Rinaldi, G., Badja, C., Degasperi, A., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.09.757935
Self-citation
- Authors
- Glodzik, D., Morganella, S., Davies, H., Simpson, P. T., Li, Y., Zou, X., Diez-Perez, J., Staaf, J., Alexandrov, L. B., Smid, M., Brinkman, A. B., Rye, I. H., Russnes, H., Raine, K., Purdie, C. A., Lakhani, S. R., Thompson, A. M., Birney, E., Stunnenberg, H. G., van de Vijver, M. J., Martens, J. W. M., Børresen-Dale, A.-L., Richardson, A. L., Kong, G., Viari, A., Easton, D., Evan, G., Campbell, P. J., Stratton, M. R., & Nik-Zainal, S.
- Affiliations
- Wellcome Sanger Institute (GB)
- The University of Queensland (AU)
- Lund University (SE)
- Los Alamos National Laboratory (US)
- Erasmus MC (NL)
- Radboud University Nijmegen (NL)
- Oslo University Hospital (NO)
- Ninewells Hospital (GB)
- The University of Texas MD Anderson Cancer Center (US)
- European Bioinformatics Institute (GB)
- Brigham and Women's Hospital (US)
- Hanyang University (KR)
- Institut national de recherche en sciences et technologies du numérique (FR)
- University of Cambridge (GB)
- ORCID
- Morganella, Sandro
- Davies, Helen
- Simpson, Peter T
- Li, Yilong
- Zou, Xueqing
- Staaf, Johan
- Alexandrov, Ludmil B
- Smid, Marcel
- Brinkman, Arie B
- Rye, Inga Hansine
- Russnes, Hege
- Raine, Keiran
- Purdie, Colin A
- Lakhani, Sunil R
- Birney, Ewan
- Stunnenberg, Hendrik G
- Martens, John W M
- Richardson, Andrea L
- Kong, Gu
- Viari, Alain
- Easton, Douglas
- Campbell, Peter J
- Stratton, Michael R
- Venue
- Nature Genetics
- Published
- 2017-01-23
- Volume
- 49
- Issue
- 3
- Pages
- 341-348
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC5988034
- OpenAlex
- W2582704504
- Cited by
- 84
- References
- 42
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 5 · 2023: 8 · 2022: 7 · 2021: 5 · 2020: 11 · 2019: 10 · 2018: 20 · 2017: 10
- FWCI
- 4.69
- Type
- journal article
- Language
- en
- Update notices
- erratum (2017-11-01)
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Lund University Publications (Lund University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Apollo
- Funders
- Wellcome Trust (077012/Z/05/Z, 101126/B/13/Z, WT100183MA, 098051)
- Cancer Research UK (12077, 22585, 19013, 20952, 23916, 22932, 23433)
- European Commission (242006)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- somatic rearrangements, tandem duplication, breast cancer, super-enhancers, mutational signatures, homologous recombination deficiency, DNA double-strand break repair, copy number variation, oncogene expression, non-coding regulatory elements
- MeSH terms
- Breast Neoplasms, DNA Repair, Female, Humans, Mutation, Regulatory Sequences, Nucleic Acid, Gene Expression, Genome, DNA Breaks, Double-Stranded, Genetic Loci, Transcriptome
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