The patterns and dynamics of genomic instability in metastatic pancreatic cancer
Open accessAbstract
Pancreatic cancer is an aggressive malignancy with a five-year mortality of 97-98%, usually due to widespread metastatic disease. Previous studies indicate that this disease has a complex genomic landscape, with frequent copy number changes and point mutations, but genomic rearrangements have not been characterized in detail. Despite the clinical importance of metastasis, there remain fundamental questions about the clonal structures of metastatic tumours, including phylogenetic relationships among metastases, the scale of ongoing parallel evolution in metastatic and primary sites, and how the tumour disseminates. Here we harness advances in DNA sequencing to annotate genomic rearrangements in 13 patients with pancreatic cancer and explore clonal relationships among metastases. We find that pancreatic cancer acquires rearrangements indicative of telomere dysfunction and abnormal cell-cycle control, namely dysregulated G1-to-S-phase transition with intact G2-M checkpoint. These initiate amplification of cancer genes and occur predominantly in early cancer development rather than the later stages of the disease. Genomic instability frequently persists after cancer dissemination, resulting in ongoing, parallel and even convergent evolution among different metastases. We find evidence that there is genetic heterogeneity among metastasis-initiating cells, that seeding metastasis may require driver mutations beyond those required for primary tumours, and that phylogenetic trees across metastases show organ-specific branches. These data attest to the richness of genetic variation in cancer, brought about by the tandem forces of genomic instability and evolutionary selection.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Pancreatic tumours are highly heterogeneous, both within and between individuals.
“Pancreatic tumours are highly heterogeneous, both within and between individuals.66,67”
From Early detection of pancreatic cancer (2020) · cites this paper as [66]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
Jones, S., Zhang, X., Parsons, D. W., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., et al. (2008) · Science · doi:10.1126/science.1164368 · Cited by 3,969 · see citing works
Self-citationMapping short DNA sequencing reads and calling variants using mapping quality scores
Li, H., Ruan, J., & Durbin, R. (2008) · Genome Research · doi:10.1101/gr.078212.108 · Cited by 2,638 · see citing works
Recurring mutations found by sequencing an acute myeloid leukemia genome
Mardis, E. R., Ding, L., Dooling, D. J., Larson, D. E., McLellan, M. D., Chen, K., Koboldt, D. C., Fulton, R. S., Delehaunty, K. D., McGrath, S. D., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0903840 · Cited by 2,219 · 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-citationTHE STABILITY OF BROKEN ENDS OF CHROMOSOMES IN ZEA MAYS
McClintock, B. (1941) · Genetics · doi:10.1093/genetics/26.2.234 · Cited by 1,610 · see citing works
Pancreatic cancer biology and genetics
Bardeesy, N. M., & DePinho, R. A. (2002) · Nature reviews. Cancer · doi:10.1038/nrc949 · Cited by 1,144 · see citing works
Parallel progression of primary tumours and metastases
Klein, C. A. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2627 · Cited by 1,134 · see citing works
Genome remodelling in a basal-like breast cancer metastasis and xenograft
Ding, L., Ellis, M. J., Li, S., Larson, D. E., Chen, K., Wallis, J. W., Harris, C. C., McLellan, M. D., Fulton, R. S., Fulton, L., et al. (2010) · Nature · doi:10.1038/nature08989 · Cited by 1,134 · 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-citationMutational evolution in a lobular breast tumour profiled at single nucleotide resolution
Shah, S. P., Morin, R. D., Khattra, J. S., Prentice, L., Pugh, T. J., Burleigh, A., Delaney, A. D., Gelmon, K. A., Guliany, R., Senz, J., et al. (2009) · Nature · doi:10.1038/nature08489 · Cited by 1,063 · see citing works
Complex 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-citationCampbell, P. J., Stephens, P. J., Pleasance, E., O’Meara, S., Li, H., Santarius, T., Stebbings, L. A., Leroy, C., Edkins, S., Hardy, C. W., et al. (2008) · Nature Genetics · doi:10.1038/ng.128 · Cited by 812 · see citing works
Self-citationGenetic determinants of cancer metastasis
Nguyen, D. X., & Massagué, J. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2101 · Cited by 796 · see citing works
Linking functional decline of telomeres, mitochondria and stem cells during ageing
Sahin, E., & DePinho, R. A. (2010) · Nature · doi:10.1038/nature08982 · Cited by 759 · see citing works
A large genome center's improvements to the Illumina sequencing system
Quail, M. A., Kozarewa, I., Smith, F., Scally, A., Stephens, P. J., Durbin, R. M., Swerdlow, H., & Turner, D. (2008) · Nature Methods · doi:10.1038/nmeth.1270 · Cited by 732 · see citing works
Self-citationCopy number analysis indicates monoclonal origin of lethal metastatic prostate cancer
Liu, W., Laitinen, S., Khan, S., Vihinen, M., Kowalski, J., Yu, G., Chen, L., Ewing, C. M., Eisenberger, M. A., Carducci, M. A., et al. (2009) · Nature Medicine · doi:10.1038/nm.1944 · Cited by 655 · see citing works
Genetic heterogeneity of single disseminated tumour cells in minimal residual cancer
Klein, C. A., Blankenstein, T. J. F., Schmidt‐Kittler, O., Petronio, M., Polzer, B. M., Stoecklein, N. H., & Riethmüller, G. (2002) · The Lancet · doi:10.1016/s0140-6736(02)09838-0 · Cited by 479 · see citing works
Gisselsson, D., Jonson, T., Petersén, Å., Strömbeck, B., Cin, P. D., Höglund, M., Mitelman, F., Mertens, F., & Mandahl, N. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.211357798 · Cited by 416 · see citing works
Kuukasjärvi, T., Karhu, R., Tanner, M., Kähkönen, M., Schäffer, A. A., Nupponen, N. N., Pennanen, S., Kallioniemi, A. H., Kallioniemi, O., & Isola, J. (1997) · PubMed · Cited by 401 · see citing works
Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers
Maser, R. S., Choudhury, B., Campbell, P. J., Feng, B., Wong, K.-K., Protopopov, A., O’Neil, J., Gutierrez, A., Ivanova, E., Perna, I., et al. (2007) · Nature · doi:10.1038/nature05886 · Cited by 377 · see citing works
Self-citationSubclonal phylogenetic structures in cancer revealed by ultra-deep sequencing
Campbell, P. J., Pleasance, E., Stephens, P. J., Dicks, E., Rance, R., Goodhead, I., Follows, G., Green, A. R., Futreal, P. A., & Stratton, M. R. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801523105 · Cited by 365 · see citing works
Self-citationFlohr, T., Schrauder, A., Cazzaniga, G., Panzer‐Grümayer, R., van der Velden, V., Fischer, S. H., Stanulla, M., Basso, G., Niggli, F. K., Schäfer, B. W., et al. (2008) · Leukemia · doi:10.1038/leu.2008.5 · Cited by 361 · see citing works
Telomere dysfunction provokes regional amplification and deletion in cancer genomes
O'Hagan, R. C., Chang, S., Maser, R. S., Mohan, R., Artandi, S. E., Chin, L., & DePinho, R. A. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00094-6 · Cited by 246 · see citing works
Replication licensing and cancer — a fatal entanglement?
Blow, J. J., & Gillespie, P. J. (2008) · Nature reviews. Cancer · doi:10.1038/nrc2500 · Cited by 229 · see citing works
Bignell, G. R., Santarius, T., Pole, J. C. M., Butler, A. P., Perry, J., Pleasance, E., Greenman, C., Menzies, A. H., Taylor, S., Edkins, S., et al. (2007) · Genome Research · doi:10.1101/gr.6522707 · Cited by 195 · see citing works
Self-citationGenomic alterations link Rho family of GTPases to the highly invasive phenotype of pancreas cancer
Kimmelman, A. C., Hezel, A. F., Aguirre, A. J., Zheng, H., Paik, J., Ying, H., Chu, G. C., Zhang, J. X., Sahin, E., Yeo, G., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809966105 · Cited by 165 · see citing works
Self-citationHarada, T., Chelala, C., Bhakta, V, Chaplin, T., Caulee, K., Baril, P., Young, B. D., & Lemoine, N. R. (2008) · Oncogene · doi:10.1038/sj.onc.1210832 · Cited by 159 · see citing works
Embuscado, E. E., Laheru, D. A., Ricci, F., Yun, K. J., Witzel, S. D. B., Seigel, A., Flickinger, K., Hidalgo, M. M., Bova, G. S., & Iacobuzio–Donahue, C. A. (2005) · Cancer Biology & Therapy · doi:10.4161/cbt.4.5.1663 · Cited by 151 · see citing works
Self-citationFrequent genomic copy number gain and overexpression of GATA-6 in pancreatic carcinoma
Fu, B., Luo, M., Lakkur, S. S., Lucito, R., & Iacobuzio–Donahue, C. A. (2008) · Cancer Biology & Therapy · doi:10.4161/cbt.7.10.6565 · Cited by 79 · see citing works
Self-citationHashimoto, Y., Murakami, Y., Uemura, K., Hayashidani, Y., Sudo, T., Ohge, H., Fukuda, E., Shimamoto, F., Sueda, T., & Hiyama, E. (2007) · Journal of Gastrointestinal Surgery · doi:10.1007/s11605-007-0383-9 · Cited by 57 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Hallmarks of Cancer: The Next Generation
Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590 · 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
Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing
Gerlinger, M., Rowan, A. J., Horswell, S., Larkin, J., Endesfelder, D., Gronroos, E., Martinez, P., Matthews, N., Stewart, A., Tarpey, P., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1113205 · Cited by 7,774 · see citing works
Self-citationRadiomics: extracting more information from medical images using advanced feature analysis
Lambin, P., Rios-Velazquez, E., Leijenaar, R., Carvalho, S., van Stiphout, R. G. P. M., Granton, P., Zegers, C. M. L., Gillies, R., Boellard, R., Dekker, A., et al. (2012) · European Journal of Cancer · doi:10.1016/j.ejca.2011.11.036 · Cited by 6,084 · see citing works
Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples
Cibulskis, K., Lawrence, M. S., Carter, S. L., Sivachenko, A., Jaffe, D. B., Sougnez, C. L., Gabriel, S., Meyerson, M. M., Lander, E. S., & Getz, G. A. (2013) · Nature Biotechnology · doi:10.1038/nbt.2514 · Cited by 4,838 · see citing works
A Perspective on Cancer Cell Metastasis
Chaffer, C. L., & Weinberg, R. A. (2011) · Science · doi:10.1126/science.1203543 · Cited by 4,791 · see citing works
Tumor Metastasis: Molecular Insights and Evolving Paradigms
Valastyan, S., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.09.024 · Cited by 4,011 · see citing works
Tumour heterogeneity and resistance to cancer therapies
Dagogo-Jack, I., & Shaw, A. T. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.166 · Cited by 3,846 · see citing works
Emerging Biological Principles of Metastasis
Lambert, A. W., Pattabiraman, D. R., & Weinberg, R. A. (2017) · Cell · doi:10.1016/j.cell.2016.11.037 · Cited by 3,075 · see citing works
Clonal heterogeneity and tumor evolution: past, present, and the future
McGranahan, N., & Swanton, C. (2017) · Cell · doi:10.1016/j.cell.2017.01.018 · Cited by 2,840 · see citing works
Whole 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
“The majority of patients with mutations in BRCA pathway genes (9) are within this intersect, however 2 have the mutational signature, but are classified either as scattered (n 5 1) or locally rearranged (n 5 1).”
BackgroundSelf-citationVincent, A., Herman, J. M., Schulick, R., Hruban, R. H., & Goggins, M. (2011) · The Lancet · doi:10.1016/s0140-6736(10)62307-0 · Cited by 2,613 · see citing works
Massive genomic rearrangement acquired in a single catastrophic event during cancer development
Stephens, P. J., Greenman, C. D., Fu, B., Yang, F., Bignell, G. R., Mudie, L. J., Pleasance, E. D., Lau, K. W., Beare, D., Stebbings, L. A., et al. (2011) · Cell · doi:10.1016/j.cell.2010.11.055 · Cited by 2,414 · see citing works
Self-citationDrug resistance in cancer: An overview
Housman, G., Byler, S., Heerboth, S., Lapinska, K., Longacre, M., Snyder, N., & Sarkar, S. (2014) · Cancers · doi:10.3390/cancers6031769 · Cited by 2,463 · see citing works
Tumour heterogeneity and cancer cell plasticity
Meacham, C., & Morrison, S. (2013) · Nature · doi:10.1038/nature12624 · Cited by 2,350 · see citing works
The causes and consequences of genetic heterogeneity in cancer evolution
Burrell, R. A., McGranahan, N., Bartek, J., & Swanton, C. (2013) · Nature · doi:10.1038/nature12625 · Cited by 2,262 · see citing works
Evolution of the Cancer Stem Cell Model
Kreso, A., & Dick, J. E. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.02.006 · Cited by 2,212 · see citing works
Organoid models of human and mouse ductal pancreatic cancer
Boj, S. F., Hwang, C.-I., Baker, L. A., Chio, I. I. C., Engle, D. D., Corbo, V., Jager, M., Ponz-Sarvise, M., Tiriac, H., Spector, M. S., et al. (2015) · Cell · doi:10.1016/j.cell.2014.12.021 · Cited by 2,150 · see citing works
Self-citationEMT and Dissemination Precede Pancreatic Tumor Formation
Rhim, A. D., Mirek, E. T., Aiello, N. M., Maitra, A., Bailey, J. M., McAllister, F., Reichert, M., Beatty, G. L., Rustgi, A. K., Vonderheide, R. H., et al. (2012) · Cell · doi:10.1016/j.cell.2011.11.025 · Cited by 2,136 · see citing works
Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes
Initiative, A. P. C. G., Biankin, A. V., Waddell, N., Kassahn, K. S., Gingras, M.-C., Muthuswamy, L. B., Johns, A. L., Miller, D. K., Wilson, P. J., Patch, A.-M., et al. (2012) · Nature · doi:10.1038/nature11547 · Cited by 2,058 · see citing works
Self-citationMetastatic colonization by circulating tumour cells
Massagué, J., & Obenauf, A. C. (2016) · Nature · doi:10.1038/nature17038 · Cited by 2,062 · see citing works
The cancer stem cell: premises, promises and challenges
Clevers, H. (2011) · Nature Medicine · doi:10.1038/nm.2304 · Cited by 1,915 · see citing works
Li, D., Xie, K., Wolff, R. A., & Abbruzzese, J. L. (2004) · The Lancet · doi:10.1016/s0140-6736(04)15841-8 · Cited by 1,715 · see citing works
The Life History of 21 Breast Cancers
Nik-Zainal, S., Van Loo, P., Wedge, D. C., Alexandrov, L. B., Greenman, C. D., Lau, K. W., Raine, K., Jones, D., Marshall, J., Ramakrishna, M., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.023 · Cited by 1,443 · see citing works
Self-citationRethinking ovarian cancer: recommendations for improving outcomes
Vaughan, S., Coward, J. I. G., Bast, R. C., Berchuck, A., Berek, J. S., Brenton, J. D., Coukos, G., Crum, C. P., Drapkin, R., Etemadmoghadam, D., et al. (2011) · Nature reviews. Cancer · doi:10.1038/nrc3144 · Cited by 1,470 · see citing works
Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia
Shlush, L. I., Zandi, S., Mitchell, A., Chen, W. C., Brandwein, J. M., Gupta, V., Kennedy, J. A., Schimmer, A. D., Schuh, A. C., Yee, K. W., et al. (2014) · Nature · doi:10.1038/nature13038 · Cited by 1,443 · see citing works
The evolutionary history of lethal metastatic prostate cancer
ICGC Prostate UK Group, Gundem, G., Loo, P. V., Kremeyer, B., Alexandrov, L. B., Tubío, J. M. C., Papaemmanuil, E., Brewer, D. S., Kallio, H. M. L., Högnäs, G., et al. (2015) · Nature · doi:10.1038/nature14347 · Cited by 1,358 · see citing works
Self-citationPeng, J., Sun, B.-F., Chen, C.-Y., Zhou, J.-Y., Chen, Y.-S., Chen, H., Liu, L., Huang, D., Jiang, J., Cui, G.-S., et al. (2019) · Cell Research · doi:10.1038/s41422-019-0195-y · Cited by 1,321 · see citing works
Forshew, T., Murtaza, M., Parkinson, C., Gale, D. G., Tsui, D. W. Y., Kaper, F., Dawson, S., Piskorz, A., Jimenez‐Liñan, M., Bentley, D., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003726 · Cited by 1,298 · see citing works
Genome-Wide Detection of Single-Nucleotide and Copy-Number Variations of a Single Human Cell
Zong, C., Lu, S., Chapman, A. R., & Xie, X. S. (2012) · Science · doi:10.1126/science.1229164 · Cited by 1,154 · see citing works
Somatic<i>SF3B1</i>Mutation in Myelodysplasia with Ring Sideroblasts
Papaemmanuil, E., Cazzola, M., Boultwood, J., Malcovati, L., Vyas, P., Bowen, D., Pellagatti, A., Wainscoat, J. S., Hellstrom-Lindberg, E., Gambacorti-Passerini, C., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1103283 · Cited by 1,222 · see citing works
Self-citationTumour heterogeneity in the clinic
Bedard, P. L., Hansen, A. R., Ratain, M. J., & Siu, L. L. (2013) · Nature · doi:10.1038/nature12627 · Cited by 1,214 · see citing works
Gerlinger, M., Horswell, S. D., Larkin, J., Rowan, A., Salm, M., Varela, I., Fisher, R. A., McGranahan, N., Matthews, N., Santos, C. R., et al. (2014) · Nature Genetics · doi:10.1038/ng.2891 · Cited by 1,211 · see citing works
Self-citationDouble indexing overcomes inaccuracies in multiplex sequencing on the Illumina platform
Kircher, M., Sawyer, S., & Meyer, M. (2012) · Nucleic Acids Research · doi:10.1093/nar/gkr771 · Cited by 1,106 · see citing works
On the Origin of Cancer Metastasis
Seyfried, T. N., & Huysentruyt, L. C. (2012) · Critical Reviews™ in Oncogenesis · doi:10.1615/critrevoncog.v18.i1-2.40 · Cited by 1,192 · see citing works
Biological and therapeutic impact of intratumor heterogeneity in cancer evolution
McGranahan, N., & Swanton, C. (2015) · Cancer Cell · doi:10.1016/j.ccell.2014.12.001 · Cited by 1,077 · see citing works
Cancer stem cells: impact, heterogeneity, and uncertainty
Magee, J. A., Piskounova, E., & Morrison, S. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.03.003 · Cited by 1,137 · see citing works
Brastianos, P. K., Carter, S. L., Santagata, S., Cahill, D. P., Taylor-Weiner, A. N., Jones, R. T., Allen, E. M. V., Lawrence, M. S., Horowitz, P. M., Cibulskis, K., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0369 · Cited by 1,084 · see citing works
The Next-Generation Sequencing Revolution and Its Impact on Genomics
Koboldt, D. C., Steinberg, K. M., Larson, D. E., Wilson, R. K., & Mardis, E. R. (2013) · Cell · doi:10.1016/j.cell.2013.09.006 · Cited by 1,039 · see citing works
Widespread Genetic Heterogeneity in Multiple Myeloma: Implications for Targeted Therapy
Lohr, J. G., Stojanov, P., Carter, S. L., Cruz-Gordillo, P., Lawrence, M. S., Auclair, D., Sougnez, C., Knoechel, B., Gould, J., Saksena, G., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2013.12.015 · Cited by 988 · see citing works
Cancer heterogeneity: implications for targeted therapeutics
Fisher, R. A., Pusztai, L., & Swanton, C. (2013) · British Journal of Cancer · doi:10.1038/bjc.2012.581 · Cited by 980 · see citing works
The lymphatic vasculature in disease
Alitalo, K. K. (2011) · Nature Medicine · doi:10.1038/nm.2545 · Cited by 964 · see citing works
Intratumor Heterogeneity: Evolution through Space and Time
Swanton, C. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-2217 · Cited by 931 · see citing works
Weichselbaum, R. R., & Hellmän, S. (2011) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2011.44 · Cited by 947 · see citing works
Evolution of Neoantigen Landscape during Immune Checkpoint Blockade in Non–Small Cell Lung Cancer
Anagnostou, V., Smith, K. N., Forde, P. M., Niknafs, N., Bhattacharya, R., White, J. R., Zhang, T., Adleff, V., Phallen, J. A., Wali, N., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0828 · Cited by 898 · see citing works
Heterogeneity 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-citationExosome-based liquid biopsies in cancer: opportunities and challenges
Wang, Y., Hurley, J. D., Roberts, D., Chakrabortty, S. K., Enderle, D., Noerholm, M., Breakefield, X. O., & Skog, J. (2021) · Annals of Oncology · doi:10.1016/j.annonc.2021.01.074 · Cited by 871 · see citing works
Patterns of somatic structural variation in human cancer genomes
Li, Y., Roberts, N. D., Wala, J. A., Shapira, O., Schumacher, S. E., Kumar, K., Khurana, E., Waszak, S., Korbel, J. O., Haber, J. E., et al. (2020) · Nature · doi:10.1038/s41586-019-1913-9 · Cited by 867 · see citing works
Self-citationTracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal
Turajlic, S., Xu, H., Litchfield, K., Rowan, A., Chambers, T., Lopez, J. I., Nicol, D. L., O’Brien, T., Larkin, J., Horswell, S. D., et al. (2018) · Cell · doi:10.1016/j.cell.2018.03.057 · Cited by 831 · see citing works
Telomeres in cancer: tumour suppression and genome instability
Maciejowski, J., & de Lange, T. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.171 · Cited by 745 · see citing works
Recurrent Somatic Structural Variations Contribute to Tumorigenesis in Pediatric Osteosarcoma
Chen, X., Bahrami, A., Pappo, A., Easton, J., Dalton, J., Hedlund, E., Ellison, D., Shurtleff, S., Wu, G., Wei, L., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.03.003 · Cited by 752 · see citing works
Tumor metastasis: moving new biological insights into the clinic
Wan, L., Pantel, K., & Kang, Y. (2013) · Nature Medicine · doi:10.1038/nm.3391 · Cited by 746 · see citing works
Huang, Y., Liu, Z., He, L., Chen, X., Pan, D., Ma, Z., Liang, C., Tian, J., & Liang, C. (2016) · Radiology · doi:10.1148/radiol.2016152234 · Cited by 741 · see citing works
Yap1 Activation Enables Bypass of Oncogenic Kras Addiction in Pancreatic Cancer
Kapoor, A., Yao, W., Ying, H., Hua, S., Liewen, A., Wang, Q., Zhong, Y., Wu, C.-J., Sadanandam, A., Hu, B., et al. (2014) · Cell · doi:10.1016/j.cell.2014.06.003 · Cited by 716 · see citing works
The Multifaceted Role of Chromosomal Instability in Cancer and Its Microenvironment
Bakhoum, S. F. W., & Cantley, L. C. (2018) · Cell · doi:10.1016/j.cell.2018.08.027 · Cited by 717 · see citing works
Chromothripsis and Kataegis Induced by Telomere Crisis
Maciejowski, J., Li, Y., Bosco, N., Campbell, P. J., & de Lange, T. (2015) · Cell · doi:10.1016/j.cell.2015.11.054 · Cited by 675 · see citing works
Self-citationTranscription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution
Chan-Seng-Yue, M., Kim, J. C., Wilson, G. W., Ng, K., Figueroa, E. F., O’Kane, G. M., Connor, A. A., Denroche, R. E., Grant, R. C., McLeod, J., et al. (2020) · Nature Genetics · doi:10.1038/s41588-019-0566-9 · Cited by 669 · see citing works
Self-citationMetastatic Stem Cells: Sources, Niches, and Vital Pathways
Óskarsson, T., Batlle, E., & Massagué, J. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.02.002 · Cited by 702 · see citing works
Exploring the Genomes of Cancer Cells: Progress and Promise
Stratton, M. R. (2011) · Science · doi:10.1126/science.1204040 · Cited by 688 · see citing works
Self-citationAung, 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
Evolution of the cancer genome
Yates, L. R., & Campbell, P. J. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3317 · Cited by 645 · see citing works
Self-citationClonal competition with alternating dominance in multiple myeloma
Keats, J. J., Chesi, M., Egan, J. B., Garbitt, V. M., Palmer, S. E., Braggio, E., Wier, S. V., Blackburn, P. R., Baker, A. S., Dispenzieri, A. A., et al. (2012) · Blood · doi:10.1182/blood-2012-01-405985 · Cited by 636 · see citing works
Metastasis as an evolutionary process
Turajlic, S., & Swanton, C. (2016) · Science · doi:10.1126/science.aaf2784 · Cited by 661 · see citing works
Dynamics of genomic clones in breast cancer patient xenografts at single-cell resolution
Eirew, P. D., Steif, A., Khattra, J. S., Ha, G., Yap, D., Farahani, H., Gelmon, K. A., Chia, S., Mar, C., Wan, A. N. C., et al. (2014) · Nature · doi:10.1038/nature13952 · Cited by 585 · see citing works
Vanharanta, S., & Massagué, J. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.09.007 · Cited by 563 · see citing works
Mechanisms Governing Metastatic Dormancy and Reactivation
Giancotti, F. G. (2013) · Cell · doi:10.1016/j.cell.2013.10.029 · Cited by 586 · see citing works
deFuse: An Algorithm for Gene Fusion Discovery in Tumor RNA-Seq Data
McPherson, A., Hormozdiari, F., Zayed, A., Giuliany, R., Ha, G., Sun, M. G. F., Griffith, M., Heravi Moussavi, A., Senz, J., Melnyk, N., et al. (2011) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1001138 · Cited by 557 · see citing works
Chromothripsis as an on-target consequence of CRISPR–Cas9 genome editing
Leibowitz, M. L., Papathanasiou, S., Doerfler, P. A., Blaine, L. J., Sun, L., Yao, Y., Zhang, C.-Z., Weiss, M. J., & Pellman, D. (2021) · Nature Genetics · doi:10.1038/s41588-021-00838-7 · Cited by 583 · see citing works
Schiavon, G., Hrebien, S., García-Murillas, I., Cutts, R. J., Pearson, A., Tarazona, N., Fenwick, K., Kozarewa, I., López‐Knowles, E., Ribas, R., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aac7551 · Cited by 589 · see citing works
Clinical management of breast cancer heterogeneity
Zardavas, D., Irrthum, A., Swanton, C., & Piccart, M. J. (2015) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2015.73 · Cited by 572 · see citing works
A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns
Notta, F., Chan-Seng-Yue, M., Lemire, M., Li, Y., Wilson, G. W., Connor, A. A., Denroche, R. E., Liang, S.-B., Brown, A. M. K., Kim, J. C., et al. (2016) · Nature · doi:10.1038/nature19823 · Cited by 528 · see citing works
Self-citationCancer stem cells: advances in knowledge and implications for cancer therapy
Chu, X., Tian, W., Ning, J., Xiao, G., Zhou, Y., Wang, Z., Zhai, Z., Tanzhu, G., Yang, J., & Zhou, R. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01851-y · Cited by 597 · see citing works
Translational Implications of Tumor Heterogeneity
Jamal‐Hanjani, M., Quezada, S. A., Larkin, J., & Swanton, C. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-1429 · Cited by 549 · see citing works
The biology of circulating tumor cells
Pantel, K., & Speicher, M. R. (2015) · Oncogene · doi:10.1038/onc.2015.192 · Cited by 544 · see citing works
Radiomics strategies for risk assessment of tumour failure in head-and-neck cancer
Vallières, M., Kay‐Rivest, E., Perrin, L. J., Liem, X., Furstoss, C., Aerts, H. J. W. L., Khaouam, N., Nguyen‐Tan, P. F., Wang, C.-S., Sultanem, K., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-10371-5 · Cited by 543 · see citing works
Criteria for Inference of Chromothripsis in Cancer Genomes
Korbel, J. O., & Campbell, P. J. (2013) · Cell · doi:10.1016/j.cell.2013.02.023 · Cited by 520 · see citing works
Self-citationMcDonald, O. G., Li, X., Saunders, T., Tryggvadottir, R., Mentch, S. J., Warmoes, M. O., Word, A. E., Carrer, A., Salz, T. H., Natsume, S., et al. (2017) · Nature Genetics · doi:10.1038/ng.3753 · Cited by 494 · see citing works
Self-citationAddressing the challenges of pancreatic cancer: Future directions for improving outcomes
Hidalgo, M. M., Cascinu, S., Kleeff, J. H., Labianca, R., Löhr, M. J., Neoptolemos, J. P., Real, F. X., Laethem, J. V., & Heinemann, V. (2014) · Pancreatology · doi:10.1016/j.pan.2014.10.001 · Cited by 507 · see citing works
Current Progress in CAR-T Cell Therapy for Solid Tumors
Ma, S., Li, X., Wang, X., Cheng, L., Li, Z., Zhang, C., Ye, Z., & Qian, Q. (2019) · International Journal of Biological Sciences · doi:10.7150/ijbs.34213 · Cited by 499 · see citing works
Rodriguez-Martin, B., Alvarez, E. G., Baez-Ortega, A., Zamora, J., Supek, F., Demeulemeester, J., Santamarina, M., Ju, Y. S., Temes, J., Garcia-Souto, D., et al. (2020) · Nature Genetics · doi:10.1038/s41588-019-0562-0 · Cited by 451 · see citing works
Self-citationQuantitative evidence for early metastatic seeding in colorectal cancer
Hu, Z., Ding, J., Ma, Z., Sun, R., Seoane, J. A., Shaffer, J. S., Suarez, C. J., Berghoff, A. S., Cremolini, C., Falcone, A., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0423-x · Cited by 480 · see citing works
Orth, M., Metzger, P., Gerum, S., Mayerle, J. V., Schneider, G., Belka, C., Schnurr, M., & Lauber, K. (2019) · Radiation Oncology · doi:10.1186/s13014-019-1345-6 · Cited by 488 · see citing works
Intratumor Heterogeneity: Seeing the Wood for the Trees
Yap, T. A., Gerlinger, M., Futreal, P. A., Pusztai, L., & Swanton, C. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003854 · Cited by 487 · see citing works
Self-citationAPOBEC Enzymes: Mutagenic Fuel for Cancer Evolution and Heterogeneity
Swanton, C., McGranahan, N., Starrett, G. J., & Harris, R. S. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0344 · Cited by 480 · see citing works
Early detection of pancreatic cancer
Pereira, S. P., Oldfield, L., Ney, A., Hart, P. A., Keane, M. G., Pandol, S. J., Li, D., Greenhalf, W., Jeon, C. Y., Koay, E. J., et al. (2020) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(19)30416-9 · Cited by 482 · see citing works
Tumor Microenvironment in Pancreatic Cancer Pathogenesis and Therapeutic Resistance
Sherman, M. H., & Beatty, G. L. (2022) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-031621-024600 · Cited by 481 · see citing works
Mlecnik, B., Bindea, G., Kirilovsky, A., Angell, H. K., Obenauf, A. C., Tosolini, M., Church, S., Maby, P., Vasaturo, A., Angelova, M., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aad6352 · Cited by 468 · see citing works
Evolution of human BCR–ABL1 lymphoblastic leukaemia-initiating cells
Notta, F., Mullighan, C. G., Wang, J. C. Y., Poeppl, A. G., Doulatov, S. R., Phillips, L. A., Ma, J., Minden, M. D., Downing, J. R., & Dick, J. E. (2011) · Nature · doi:10.1038/nature09733 · Cited by 459 · see citing works
Break-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 462 · see citing works
Enhancer Reprogramming Promotes Pancreatic Cancer Metastasis
Roe, J., Hwang, C., Somerville, T. D. D., Milazzo, J. P., Lee, E. J., Silva, B. D., Maiorino, L., Tiriac, H., Young, C. M., Miyabayashi, K., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.007 · Cited by 458 · see citing works
Genetic heterogeneity and cancer drug resistance
Turner, N. C., & Reis-Filho, J. S. (2012) · The Lancet Oncology · doi:10.1016/s1470-2045(11)70335-7 · Cited by 451 · see citing works
Next-Generation Sequencing in Oncology: Genetic Diagnosis, Risk Prediction and Cancer Classification
Kamps, R., Brandão, R. D., van den Bosch, B. J. C., Paulussen, A. D. C., Xanthoulea, S., Blok, M. J., & Romano, A. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18020308 · Cited by 454 · see citing works
Lin, X., & DeAngelis, L. M. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.60.9503 · Cited by 448 · see citing works
Extensive transduction of nonrepetitive DNA mediated by L1 retrotransposition in cancer genomes
Tubio, J. M. C., Li, Y., Ju, Y. S., Martincorena, I., Cooke, S. L., Tojo, M., Gundem, G., Pipinikas, C. P., Zamora, J., Raine, K., et al. (2014) · Science · doi:10.1126/science.1251343 · Cited by 412 · see citing works
Self-citationBrain malignancies: Glioblastoma and brain metastases
Lah, T. T., Novak, M., & Breznik, B. (2019) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2019.10.010 · Cited by 443 · see citing works
A metastasis map of human cancer cell lines
Jin, X., Demere, Z., Nair, K., Ali, A., Ferraro, G. B., Natoli, T. E., Deik, A., Petronio, L., Tang, A. A., Zhu, C., et al. (2020) · Nature · doi:10.1038/s41586-020-2969-2 · Cited by 431 · see citing works
Lüönd, F., Tiede, S., & Christofori, G. (2021) · British Journal of Cancer · doi:10.1038/s41416-021-01328-7 · Cited by 442 · see citing works
Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes
Mueller, S., Engleitner, T., Maresch, R., Zukowska, M., Lange, S., Kaltenbacher, T., Konukiewitz, B., Öllinger, R., Zwiebel, M., Strong, A., et al. (2018) · Nature · doi:10.1038/nature25459 · Cited by 419 · see citing works
Self-citationPancreatic cancer biology and genetics from an evolutionary perspective
Makohon-Moore, A. P., & Iacobuzio–Donahue, C. A. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.66 · Cited by 430 · see citing works
Self-citationTumour heterogeneity and the evolution of polyclonal drug resistance
Burrell, R. A., & Swanton, C. (2014) · Molecular Oncology · doi:10.1016/j.molonc.2014.06.005 · Cited by 417 · see citing works
- Authors
- Campbell, P. J., Yachida, S., Mudie, L. J., Stephens, P. J., Pleasance, E. D., Stebbings, L. A., Morsberger, L. A., Latimer, C., McLaren, S., Lin, M.-L., McBride, D. J., Varela, I., Nik-Zainal, S. A., Leroy, C., Jia, M., Menzies, A., Butler, A. P., Teague, J. W., Griffin, C. A., Burton, J., Swerdlow, H., Quail, M. A., Stratton, M. R., Iacobuzio-Donahue, C., & Futreal, P. A.
- Affiliations
- University of Cambridge (GB)
- Johns Hopkins University (US)
- Wellcome Sanger Institute (GB)
- Institute of Cancer Research (GB)
- Corresponding author
- Futreal, P. Andrew
- ORCID
- Venue
- Nature
- Published
- 2010-10
- Volume
- 467
- Issue
- 7319
- Pages
- 1109-1113
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3137369
- OpenAlex
- W2066254965
- Cited by
- 1,317
- References
- 30
- Citations by year
- 2026: 10 · 2025: 31 · 2024: 33 · 2023: 51 · 2022: 47 · 2021: 86 · 2020: 69 · 2019: 72 · 2018: 75 · 2017: 117 · 2016: 104 · 2015: 119 · 2014: 153 · 2013: 109 · 2012: 135
- FWCI
- 34.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Skip Viragh Foundation
- Uehara Memorial Foundation
- Wellcome Trust (077012/Z/05/Z, 088340, 093867, WT088340MA)
- National Institutes of Health
- National Cancer Institute (R01CA140599, K08CA106610, CA140599, CA106610)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- pancreatic cancer, metastasis, genomic instability, chromosomal rearrangements, clonal evolution, telomere dysfunction, G1/S checkpoint, copy number alterations, tumor progression, early detection, therapeutic target, interpatient heterogeneity, tumour dissemination, somatic mutations, GATA4, GATA3
- MeSH terms
- Adenocarcinoma, Cell Cycle, Clone Cells, DNA Mutational Analysis, Humans, Liver Neoplasms, Lung Neoplasms, Neoplasm Metastasis, Organ Specificity, Pancreatic Neoplasms, Mutagenesis, Telomere, Disease Progression, Cell Lineage, Evolution, Molecular, Genomic Instability, Genes, Neoplasm
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
