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Precancerous neoplastic cells can move through the pancreatic ductal system
Open accessAbstract
Most adult carcinomas develop from noninvasive precursor lesions, a progression that is supported by genetic analysis. However, the evolutionary and genetic relationships among co-existing lesions are unclear. Here we analysed the somatic variants of pancreatic cancers and precursor lesions sampled from distinct regions of the same pancreas. After inferring evolutionary relationships, we found that the ancestral cell had initiated and clonally expanded to form one or more lesions, and that subsequent driver gene mutations eventually led to invasive pancreatic cancer. We estimate that this multi-step progression generally spans many years. These new data reframe the step-wise progression model of pancreatic cancer by illustrating that independent, high-grade pancreatic precursor lesions observed in a single pancreas often represent a single neoplasm that has colonized the ductal system, accumulating spatial and genetic divergence over time.
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“Recent phylogenetic analyses of precursor lesions from the pancreata of patients with established cancer have confirmed the stepwise progression model and accumulation of genetic alterations in the transition from PanINs to PDAC postulated using more rudimentary techniques26.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [26]
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Metadata
- Authors
- Makohon-Moore, A. P., Matsukuma, K., Zhang, M., Reiter, J. G., Gerold, J. M., Jiao, Y., Sikkema, L., Attiyeh, M. A., Yachida, S., Sandone, C., Hruban, R. H., Klimstra, D. S., Papadopoulos, N., Nowak, M. A., Kinzler, K. W., Vogelstein, B., & Iacobuzio-Donahue, C. A.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- University of California, Davis (US)
- Johns Hopkins University (US)
- Harvard University (US)
- The University of Osaka (JP)
- Howard Hughes Medical Institute (US)
- ORCID
- Venue
- Nature
- Published
- 2018-09
- Volume
- 561
- Issue
- 7722
- Pages
- 201-205
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6342205
- OpenAlex
- W2888908131
- Cited by
- 120
- References
- 47
- Citations by year
- 2026: 13 · 2025: 7 · 2024: 14 · 2023: 17 · 2022: 13 · 2021: 13 · 2020: 20 · 2019: 19 · 2018: 3
- FWCI
- 4.15
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (acceptedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Lustgarten Foundation
- Virginia and D.K. Ludwig Fund for Cancer Research
- Rolfe Pancreatic Cancer Foundation
- Austrian Science Fund (J 3996)
- National Institutes of Health (CA062924)
- National Cancer Institute (T32CA067751, T32CA160001, F31CA180682, P50CA062924, P30CA008748)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- pancreatic cancer, pancreatic precursor lesions, somatic mutations, clonal evolution, tumor progression, pancreatic ductal system, tumor heterogeneity, driver mutations
- MeSH terms
- Exome Sequencing, Humans, Models, Biological, Neoplasm Invasiveness, Pancreatic Ducts, Pancreatic Neoplasms, Precancerous Conditions, Time Factors, Mutagenesis, Disease Progression, Cell Lineage, Evolution, Molecular, Polymorphism, Single Nucleotide, Carcinoma, Pancreatic Ductal, INDEL Mutation
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