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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 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]
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“Pancreatic tumours are highly heterogeneous, both within and between individuals.66,67”
From Early detection of pancreatic cancer (2020) · cites this paper as [67]
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“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
Genetic instabilities in human cancers
Lengauer, C., Kinzler, K. W., & Vogelstein, B. (1998) · Nature · doi:10.1038/25292 · Cited by 4,168
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
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
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 2,716
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
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 827
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
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
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
Self-citationLord, B. I. (1978) · British Journal of Cancer · doi:10.1038/bjc.1978.97 · Cited by 669
Emerging molecular markers of cancer
Sidransky, D. (2002) · Nature Reviews Cancer · doi:10.1038/nrc755 · Cited by 662
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 519
Self-citationHigh-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
A 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
Critical determinants of metastasis
Fidler, I. J. (2002) · Seminars in Cancer Biology · doi:10.1006/scbi.2001.0416 · Cited by 415
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
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
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
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
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
Terada, T., Ohta, T., Kitamura, Y., Ashida, K., & Matsunaga, Y. (1998) · PubMed · Cited by 47
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
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
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Hanahan, D., & Weinberg, R. A. (2011) · Cell · doi:10.1016/j.cell.2011.02.013 · Cited by 66,590
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Gillies, R. J., Kinahan, P. E., & Hricak, H. (2016) · Radiology · doi:10.1148/radiol.2015151169 · Cited by 8,421
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
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
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
“It is known that multiple subclonal populations coexist within tumours, reflecting extensive intratumoral ‘somatic evolution’ 15,16 .”
Background
Metadata
- 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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