Distant metastasis occurs late during the genetic evolution of pancreatic cancer
Open accessAbstract
Metastasis, the dissemination and growth of neoplastic cells in an organ distinct from that in which they originated, is the most common cause of death in cancer patients. This is particularly true for pancreatic cancers, where most patients are diagnosed with metastatic disease and few show a sustained response to chemotherapy or radiation therapy. Whether the dismal prognosis of patients with pancreatic cancer compared to patients with other types of cancer is a result of late diagnosis or early dissemination of disease to distant organs is not known. Here we rely on data generated by sequencing the genomes of seven pancreatic cancer metastases to evaluate the clonal relationships among primary and metastatic cancers. We find that clonal populations that give rise to distant metastases are represented within the primary carcinoma, but these clones are genetically evolved from the original parental, non-metastatic clone. Thus, genetic heterogeneity of metastases reflects that within the primary carcinoma. A quantitative analysis of the timing of the genetic evolution of pancreatic cancer was performed, indicating at least a decade between the occurrence of the initiating mutation and the birth of the parental, non-metastatic founder cell. At least five more years are required for the acquisition of metastatic ability and patients die an average of two years thereafter. These data provide novel insights into the genetic features underlying pancreatic cancer progression and define a broad time window of opportunity for early detection to prevent deaths from metastatic disease.
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Modeling studies on mutational data estimate that multistep progression to invasive pancreatic neoplasia spans multiple years, providing a wide window for early detection.
“modeling studies performed on the mutational data have estimated that the timeline of multistep progression to invasive neoplasia in the pancreas likely spans multiple years and provides a theoretically wide window of opportunity for early detection27.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [27]
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 [67]
Most clinically relevant solid tumors are highly heterogeneous at the phenotypic, physiologic, and genomic levels and continue to evolve over time.
“It is now appreciated that most clinically relevant solid tumors are highly heterogeneous at the phenotypic, physiologic, and genomic levels (13–15) and that they continue to evolve over time.”
From Radiomics: Images Are More than Pictures, They Are Data (2016) · cites this paper as [13]
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Cites
Spencer, P. M., Cameron, J. L., & Lin, L. (2000) · Cited by 7,202 · see citing works
Genetic instabilities in human cancers
Lengauer, C., Kinzler, K. W., & Vogelstein, B. (1998) · Nature · doi:10.1038/25292 · Cited by 4,168 · see citing works
Self-citationCore 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-citationOlive, K. P., Jacobetz, M. A., Davidson, C. J., Gopinathan, A., McIntyre, D., Honess, D., Madhu, B., Goldgraben, M. A., Caldwell, M. E., Allard, D., et al. (2009) · Science · doi:10.1126/science.1171362 · Cited by 3,170 · see citing works
Self-citationMetastasis: from dissemination to organ-specific colonization
Nguyen, D. X., Bos, P. D., & Massagué, J. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2622 · Cited by 2,637 · see citing works
Isaacson, P. G., Doǧan, A., Price, S. K., & Spencer, J. (1989) · The American Journal of Surgical Pathology · doi:10.1097/00000478-198912000-00004 · Cited by 1,913 · see citing works
Comparative lesion sequencing provides insights into tumor evolution
Jones, S., Chen, W.-D. D., Parmigiani, G., Diehl, F., Beerenwinkel, N., Tibor Antal, A., Traulsen, A., Nowak, M. A., Siegel, C., Velculescu, V. E., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712345105 · Cited by 817 · see citing works
Self-citationAdvanced pancreatic carcinoma: current treatment and future challenges
Stathis, A., & Moore, M. J. (2010) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2009.236 · Cited by 791 · see citing works
Signatures of mutation and selection in the cancer genome
Bignell, G. R., Greenman, C. D., Davies, H., Butler, A. P., Edkins, S., Andrews, J. M., Buck, G., Chen, L., Beare, D., Latimer, C., et al. (2010) · Nature · doi:10.1038/nature08768 · Cited by 707 · see citing works
Self-citationMaitra, A., & Hruban, R. H. (2008) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathmechdis.3.121806.154305 · Cited by 707 · see citing works
Self-citationLord, B. I. (1978) · British Journal of Cancer · doi:10.1038/bjc.1978.97 · Cited by 669 · see citing works
Emerging molecular markers of cancer
Sidransky, D. (2002) · Nature Reviews Cancer · doi:10.1038/nrc755 · Cited by 662 · see citing works
High-resolution genomic profiling of chromosomal aberrations using Infinium whole-genome genotypingPreprint
Peiffer, D. A., Le, J. M., Steemers, F. J., Chang, W., Jenniges, T., Garcia, F., Haden, K., Li, J., Shaw, C. A., Belmont, J. W., et al. (2006) · Genome Research · doi:10.1101/gr.5402306 · Cited by 519 · see citing works
Development of Personalized Tumor Biomarkers Using Massively Parallel Sequencing
Leary, R. J., Kinde, I., Diehl, F., Schmidt, K., Clouser, C., Duncan, C., Antipova, A. A., Lee, C. C., McKernan, K. J., Vega, F. M. D. L., et al. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3000702 · Cited by 517 · see citing works
Self-citationA model of human tumor dormancy: an angiogenic switch from the nonangiogenic phenotype
Naumov, G. N., Bender, E., Zurakowski, D., Kang, S.-Y., Sampson, D., Flynn, E., Watnick, R. S., Straume, O., Akslen, L. A., Folkman, J., et al. (2006) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djj068 · Cited by 423 · see citing works
Critical determinants of metastasis
Fidler, I. J. (2002) · Seminars in Cancer Biology · doi:10.1006/scbi.2001.0416 · Cited by 415 · see citing works
The Pathology and Genetics of Metastatic Pancreatic Cancer
Yachida, S., & Iacobuzio–Donahue, C. A. (2009) · Archives of Pathology & Laboratory Medicine · doi:10.5858/133.3.413 · Cited by 269 · see citing works
Self-citationRelationship between labeling indices of KI-67 and brdurd in human malignant tumors
Sasaki, K., Matsumura, K., Tsuji, T., Shinozaki, F., & Takahashi, M. (1988) · Cancer · doi:10.1002/1097-0142(19880901)62:5 · Cited by 172 · 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-citationCell production rates in human tissues and tumours and their significance. Part II: clinical data
Rew, D. A., & Wilson, G. D. (2000) · European Journal of Surgical Oncology · doi:10.1053/ejso.1999.0907 · Cited by 131 · see citing works
The time of occurrence of liver metastasis in carcinoma of the pancreas
Amikura, K., Kobari, M., & Matsuno, S. (1995) · International Journal of Pancreatology · doi:10.1007/bf02788531 · Cited by 96 · see citing works
Terada, T., Ohta, T., Kitamura, Y., Ashida, K., & Matsunaga, Y. (1998) · PubMed · Cited by 47 · see citing works
Fu, B., Guo, M., Wang, S., Campagna, D., Luo, M., Herman, J. G., & Iacobuzio–Donahue, C. A. (2007) · Cancer Biology & Therapy · doi:10.4161/cbt.6.10.4708 · Cited by 40 · see citing works
Self-citationGrowth process of small pancreatic carcinoma: A case report with imaging observation for 22 months
Hisa, T., Ohkubo, H., Shiozawa, S., Ishigame, H., Takamatsu, M., Furutake, M., Nobukawa, B., & Suda, K. (2008) · World Journal of Gastroenterology · doi:10.3748/wjg.14.1958 · Cited by 9 · 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
Radiomics: Images Are More than Pictures, They Are Data
Gillies, R. J., Kinahan, P. E., & Hricak, H. (2016) · Radiology · doi:10.1148/radiol.2015151169 · Cited by 8,421 · 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
Self-citationIntratumor 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
Decoding tumour phenotype by noninvasive imaging using a quantitative radiomics approach
Aerts, H. J. W. L., Velazquez, E. R., Leijenaar, R. T. H., Parmar, C., Grossmann, P., Carvalho, S., Bussink, J., Monshouwer, R., Haibe-Kains, B., Rietveld, D., et al. (2014) · Nature Communications · doi:10.1038/ncomms5006 · Cited by 5,132 · see citing works
“It is known that multiple subclonal populations coexist within tumours, reflecting extensive intratumoral ‘somatic evolution’ 15,16 .”
BackgroundSingle-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma
Patel, A. P., Tirosh, I., Trombetta, J. J., Shalek, A. K., Gillespie, S. M., Wakimoto, H., Cahill, D. P., Nahed, B. V., Curry, W. T., Martuza, R. L., et al. (2014) · Science · doi:10.1126/science.1254257 · Cited by 5,063 · 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
Greaves, M., & Maley, C. C. (2012) · Nature · doi:10.1038/nature10762 · Cited by 3,162 · 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
Glypican-1 identifies cancer exosomes and detects early pancreatic cancer
Melo, S. A., Luecke, L. B., Kahlert, C., Fernandez, A. F., Gammon, S. T., Kaye, J., LeBleu, V. S., Mittendorf, E. A., Weitz, J., Rahbari, N., et al. (2015) · Nature · doi:10.1038/nature14581 · Cited by 2,880 · see citing works
Tumour evolution inferred by single-cell sequencing
Navin, N., Kendall, J., Troge, J., Andrews, P., Rodgers, L., McIndoo, J., Cook, K., Stepansky, A., Levy, D., Esposito, D., et al. (2011) · Nature · doi:10.1038/nature09807 · Cited by 2,598 · see citing works
Vincent, A., Herman, J. M., Schulick, R., Hruban, R. H., & Goggins, M. (2011) · The Lancet · doi:10.1016/s0140-6736(10)62307-0 · Cited by 2,612 · see citing works
Self-citationTumour heterogeneity and cancer cell plasticity
Meacham, C., & Morrison, S. (2013) · Nature · doi:10.1038/nature12624 · Cited by 2,350 · see citing works
Moffitt, R. A., Marayati, R., Flate, E. L., Volmar, K. E., Loeza, S. G. H., Hoadley, K. A., Rashid, N. U., Williams, L. A., Eaton, S. C., Chung, A. H., et al. (2015) · Nature Genetics · doi:10.1038/ng.3398 · Cited by 2,194 · see citing works
Self-citationThe 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
EMT 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
Absolute quantification of somatic DNA alterations in human cancer
Carter, S. L., Cibulskis, K., Helman, E., McKenna, A., Shen, H., Zack, T. I., Laird, P. W., Onofrio, R. C., Winckler, W., Weir, B. A., et al. (2012) · Nature Biotechnology · doi:10.1038/nbt.2203 · Cited by 2,003 · see citing works
Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing
Ding, L., Ley, T. J., Larson, D. E., Miller, C. A., Koboldt, D. C., Welch, J. S., Ritchey, J. K., Young, M. A., Lamprecht, T., McLellan, M. D., et al. (2012) · Nature · doi:10.1038/nature10738 · Cited by 1,993 · see citing works
Intra-tumour heterogeneity: a looking glass for cancer?
Marusyk, A., Almendro, V., & Polyák, K. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3261 · Cited by 2,003 · see citing works
Kleeff, J., Korc, M., Apte, M., La Vecchia, C., Johnson, C. D., Biankin, A. V., Neale, R. E., Tempero, M., Tuveson, D. A., Hruban, R. H., et al. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.22 · Cited by 1,982 · see citing works
Self-citationThe cancer stem cell: premises, promises and challenges
Clevers, H. (2011) · Nature Medicine · doi:10.1038/nm.2304 · Cited by 1,915 · see citing works
Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics
Sottoriva, A., Spiteri, I., Piccirillo, S. G. M., Touloumis, A., Collins, V. P., Marioni, J. C., Curtis, C., Watts, C., & Tavaré, S. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1219747110 · Cited by 1,737 · see citing works
Patient-Derived Xenograft Models: An Emerging Platform for Translational Cancer Research
Hidalgo, M. M., Amant, F. C., Biankin, A. V., Budínská, E., Byrne, A. T., Caldas, C., Clarke, R. B., de Jong, S., Jonkers, J., Mælandsmo, G. M., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0001 · Cited by 1,759 · 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 1,719 · 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
Feng, Y., Spezia, M., Huang, S., Yuan, C., Zeng, Z., Zhang, L., Ji, X., Liu, W., Huang, B., Luo, W., et al. (2018) · Genes & Diseases · doi:10.1016/j.gendis.2018.05.001 · Cited by 1,537 · see citing works
Rethinking 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
Metabolic pathways promoting cancer cell survival and growth
Boroughs, L. K., & DeBerardinis, R. J. (2015) · Nature Cell Biology · doi:10.1038/ncb3124 · Cited by 1,459 · 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
Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma
Johnson, B. E., Mazor, T., Hong, C., Barnes, M., Aihara, K., McLean, C. Y., Fouse, S. D., Yamamoto, S., Ueda, H., Tatsuno, K., et al. (2014) · Science · doi:10.1126/science.1239947 · Cited by 1,362 · see citing works
Self-citationSteeg, P. S. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.25 · Cited by 1,363 · see citing works
The Cancer Stem Cell Niche: How Essential Is the Niche in Regulating Stemness of Tumor Cells?
Plaks, V., Kong, N., & Werb, Z. (2015) · Cell Stem Cell · doi:10.1016/j.stem.2015.02.015 · Cited by 1,557 · 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
Hepatocellular carcinoma: clinical frontiers and perspectives
Bruix, J., Gores, G. J., & Mazzaferro, V. (2014) · Gut · doi:10.1136/gutjnl-2013-306627 · Cited by 1,367 · see citing works
Pancreatic cancer: Advances and challenges
Halbrook, C. J., Lyssiotis, C. A., Pasca di Magliano, M., & Maitra, A. (2023) · Cell · doi:10.1016/j.cell.2023.02.014 · Cited by 1,321 · see citing works
Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Ducreux, M. P., Cunha, A. S., Caramella, C., Hollebecque, A., Burtin, P. C., Goèré, D., Seufferlein, T. T. W., Haustermans, K. M., Laethem, J. V., Conroy, T., et al. (2015) · Annals of Oncology · doi:10.1093/annonc/mdv295 · Cited by 1,297 · see citing works
Single-cell sequencing-based technologies will revolutionize whole-organism science
Shapiro, E., Biezuner, T., & Linnarsson, S. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3542 · Cited by 1,177 · 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
Tumour 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
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
CancerSEA: a cancer single-cell state atlas
Yuan, H., Yan, M., Zhang, G., Liu, W., Deng, C., Liao, G., Xu, L., Luo, T., Yan, H., Long, Z., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky939 · Cited by 1,036 · see citing works
Heterogeneity in breast cancer
Polyák, K. (2011) · Journal of Clinical Investigation · doi:10.1172/jci60534 · Cited by 1,012 · 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
Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing
Zhang, J., Fujimoto, J., Zhang, J., Wedge, D. C., Song, X., Zhang, J., Seth, S., Chow, C.-W., Cao, Y., Gumbs, C., et al. (2014) · Science · doi:10.1126/science.1256930 · Cited by 965 · see citing works
Langley, R. R., & Fidler, I. J. (2011) · International Journal of Cancer · doi:10.1002/ijc.26031 · Cited by 958 · 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
Cancer Epigenetics: Tumor Heterogeneity, Plasticity of Stem-like States, and Drug Resistance
Easwaran, H., Tsai, H.-C., & Baylin, S. B. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.05.015 · Cited by 915 · 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
Self-citationCancer Stem Cells: Basic Concepts and Therapeutic Implications
Nassar, D., & Blanpain, C. (2016) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044438 · Cited by 869 · see citing works
Pancreatic Cancer: Pathogenesis, Screening, Diagnosis, and Treatment
Wood, L. D., Canto, M. I., Jaffee, E. M., & Simeone, D. M. (2022) · Gastroenterology · doi:10.1053/j.gastro.2022.03.056 · Cited by 875 · see citing works
Tracking 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
Tumour evolution in hepatocellular carcinoma
Craig, A. J., von Felden, J., García‐Lezana, T., Sarcognato, S., & Villanueva, A. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0229-4 · Cited by 825 · see citing works
Subclonal diversification of primary breast cancer revealed by multiregion sequencing
Yates, L. R., Gerstung, M., Knappskog, S., Desmedt, C., Gundem, G., Loo, P. V., Aas, T., Alexandrov, L. B., Larsimont, D., Davies, H., et al. (2015) · Nature Medicine · doi:10.1038/nm.3886 · Cited by 812 · see citing works
Canto, M. I., Harinck, F., Hruban, R. H., Offerhaus, G. J., Poley, J.-W., Kamel, I., Nio, Y., Schulick, R. S., Bassi, C., Kluijt, I., et al. (2013) · Gut · doi:10.1136/gutjnl-2012-303108 · Cited by 784 · see citing works
Self-citationHigh grade serous ovarian carcinomas originate in the fallopian tube
Labidi‐Galy, S. I., Papp, E., Hallberg, D. L., Niknafs, N., Adleff, V., Noë, M., Bhattacharya, R., Novak, M., Jones, S., Phallen, J. A., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00962-1 · Cited by 762 · see citing works
Self-citationTumor 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
Guidelines for Validation of Next-Generation Sequencing–Based Oncology Panels
Jennings, L. J., Arcila, M. E., Corless, C. L., Kamel‐Reid, S., Lubin, I. M., Pfeifer, J. D., Temple‐Smolkin, R., Voelkerding, K. V., & Nikiforova, M. N. (2017) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2017.01.011 · Cited by 744 · see citing works
Kumar, A., Coleman, I. M., Morrissey, C. M., Zhang, X., True, L. D., Gulati, R., Etzioni, R., Bolouri, H., Montgomery, B., White, T. A., et al. (2016) · Nature Medicine · doi:10.1038/nm.4053 · Cited by 732 · see citing works
ACG Clinical Guideline: Diagnosis and Management of Pancreatic Cysts
Elta, G. H., Enestvedt, B. K., Sauer, B. G., & Lennon, A. M. (2018) · The American Journal of Gastroenterology · doi:10.1038/ajg.2018.14 · Cited by 726 · see citing works
Clonal evolution of preleukemic hematopoietic stem cells precedes human acute myeloid leukemia
Jan, M., Snyder, T. M., Corces-Zimmerman, M. R., Vyas, P., Weissman, I. L., Quake, S. R., & Majeti, R. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3004315 · Cited by 721 · see citing works
Metastatic 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
Mosaic Amplification of Multiple Receptor Tyrosine Kinase Genes in Glioblastoma
Snuderl, M., Fazlollahi, L., Le, L. P., Nitta, M., Zhelyazkova, B. H., Davidson, C. J., Akhavanfard, S., Cahill, D. P., Aldape, K., Betensky, R. A., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.11.005 · Cited by 708 · 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
Evolutionary dynamics of carcinogenesis and why targeted therapy does not work
Gillies, R. J., Verduzco, D., & Gatenby, R. A. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3298 · Cited by 677 · see citing works
Mayers, J. R., Wu, C. H., Clish, C. B., Kraft, P., Torrence, M. E., Fiske, B. P., Yuan, C., Bao, Y., Townsend, M. K., Tworoger, S. S., et al. (2014) · Nature Medicine · doi:10.1038/nm.3686 · Cited by 652 · see citing works
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
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
Desmoplasia in Primary Tumors and Metastatic Lesions of Pancreatic Cancer
Whatcott, C. J., Diep, C. H., Jiang, P., Watanabe, A. T., Lobello, J. R., Chao Sima, A., Hostetter, G. H., Shepard, H. M., Hoff, D. D. V., & Han, H. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-1051 · Cited by 646 · see citing works
Clonal 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
Molecular analysis of circulating tumour cells—biology and biomarkers
Krebs, M., Metcalf, R. L., Carter, L., Brady, G., Blackhall, F. H., & Dive, C. (2014) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2013.253 · Cited by 620 · see citing works
Zang, Z. J., Cutcutache, I., Poon, S. L., Zhang, S. L., McPherson, J. R., Tao, J., Rajasegaran, V., Heng, H. L., Deng, N., Gan, A., et al. (2012) · Nature Genetics · doi:10.1038/ng.2246 · Cited by 614 · see citing works
Tumour heterogeneity and metastasis at single-cell resolution
Lawson, D. A., Kessenbrock, K., Davis, R. T., Pervolarakis, N., & Werb, Z. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0236-7 · Cited by 606 · 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
Vanharanta, S., & Massagué, J. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.09.007 · Cited by 563 · see citing works
Applications of single-cell sequencing in cancer research: progress and perspectives
Lei, Y., Tang, R., Xu, J., Wang, W., Zhang, B., Liu, J., Yu, X., & Shi, S. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01105-2 · Cited by 597 · see citing works
Single-Cell Exome Sequencing and Monoclonal Evolution of a JAK2-Negative Myeloproliferative Neoplasm
Hou, Y., Song, L., Zhu, P., Zhang, B., Tao, Y., Xu, X., Li, F., Wu, K., Liang, J., Shao, D., et al. (2012) · Cell · doi:10.1016/j.cell.2012.02.028 · Cited by 541 · 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
Ma, X., Buscaglia, L. E. B., Barker, J. R., & Li, Y. (2011) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjr007 · Cited by 582 · 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
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
McDonald, 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-citationYachida, S., Vakiani, E., White, C. M., Zhong, Y., Saunders, T., Morgan, R., de Wilde, R. F., Maitra, A., Hicks, J. L., Marzo, A. M. D., et al. (2012) · The American Journal of Surgical Pathology · doi:10.1097/pas.0b013e3182417d36 · Cited by 536 · see citing works
Self-citationLee, J. H., Daugharthy, E. R., Scheiman, J., Kalhor, R., Ferrante, T. C., Terry, R., Turczyk, B. M., Yang, J. L., Lee, H. S., Aach, J., et al. (2015) · Nature Protocols · doi:10.1038/nprot.2014.191 · Cited by 529 · see citing works
Genetics and biology of pancreatic ductal adenocarcinoma
Ying, H., Dey, P., Yao, W., Kimmelman, A. C., Draetta, G. F., Maitra, A., & DePinho, R. A. (2016) · Genes & Development · doi:10.1101/gad.275776.115 · Cited by 527 · see citing works
Stoffel, E. M., Brand, R. E., & Goggins, M. (2023) · Gastroenterology · doi:10.1053/j.gastro.2023.02.012 · Cited by 540 · see citing works
Quantitative Imaging in Cancer Evolution and Ecology
Gatenby, R. A., Grove, O., & Gillies, R. J. (2013) · Radiology · doi:10.1148/radiol.13122697 · Cited by 515 · see citing works
Addressing 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
Genomic and phenotypic heterogeneity in prostate cancer
Haffner, M. C., Zwart, W. T., Roudier, M. P., True, L. D., Nelson, W. G., Epstein, J. I., Marzo, A. M. D., Nelson, P. S., & Yegnasubramanian, S. (2020) · Nature Reviews Urology · doi:10.1038/s41585-020-00400-w · Cited by 520 · see citing works
Cellular Heterogeneity and Molecular Evolution in Cancer
Almendro, V., Marusyk, A., & Polyák, K. (2012) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-020712-163923 · Cited by 491 · see citing works
Tracking the clonal origin of lethal prostate cancer
Haffner, M. C., Mosbruger, T. L., Esopi, D., Fedor, H. L., Heaphy, C. M., Walker, D. A., Adejola, N., Gurel, M., Hicks, J. L., Meeker, A. K., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci70354 · Cited by 498 · see citing works
Regulation of EMT in Colorectal Cancer: A Culprit in Metastasis
Vu, T., & Datta, P. K. (2017) · Cancers · doi:10.3390/cancers9120171 · Cited by 496 · see citing works
Quantitative 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
- Authors
- Yachida, S., Jones, S., Bozic, I., Antal, T., Leary, R., Fu, B., Kamiyama, M., Hruban, R. H., Eshleman, J. R., Nowak, M. A., Velculescu, V. E., Kinzler, K. W., Vogelstein, B., & Iacobuzio-Donahue, C. A.
- Affiliations
- Johns Hopkins University (US)
- Howard Hughes Medical Institute (US)
- Harvard University (US)
- ORCID
- Venue
- Nature
- Published
- 2010-10
- Volume
- 467
- Issue
- 7319
- Pages
- 1114-1117
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3148940
- OpenAlex
- W2169895148
- Cited by
- 2,502
- References
- 24
- Citations by year
- 2026: 73 · 2025: 84 · 2024: 76 · 2023: 105 · 2022: 122 · 2021: 165 · 2020: 157 · 2019: 147 · 2018: 176 · 2017: 218 · 2016: 208 · 2015: 237 · 2014: 224 · 2013: 182 · 2012: 197
- FWCI
- 50.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (5r01ca121113-15)
- U.S. Public Health Service (A62924)
- National Cancer Institute (R01CA140599, CA 57345, R01-CA121113, CA-121113, CA43460, K08CA106610, R37CA043460, R01CA057345, CA106610, P50CA062924, R37CA057345)
- National Institute of General Medical Sciences (R01GM078986, GM078986)
- 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, distant metastasis, clonal evolution, tumor subclones, chromosomal rearrangements, genomic instability, early detection, tumor heterogeneity, therapeutic target
- MeSH terms
- Adenocarcinoma, Autopsy, Clone Cells, DNA Mutational Analysis, Humans, Liver Neoplasms, Lung Neoplasms, Models, Biological, Mutation, Neoplasm Metastasis, Pancreas, Pancreatic Neoplasms, Peritoneal Neoplasms, Time Factors, Disease Progression, Cell Lineage, Evolution, Molecular, Early Detection of Cancer
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