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Nature. 2018 Sep;561(7722):201-205. doi: 10.1038/s41586-018-0481-8. Epub 2018 Sep 3.

Precancerous neoplastic cells can move through the pancreatic ductal system.

Author information

1
The David M. Rubenstein Center for Pancreatic Cancer Research, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
2
Department of Pathology, University of California, Davis, Sacramento, CA, USA.
3
The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
4
Canary Center for Cancer Early Detection, Department of Radiology, Stanford University School of Medicine, Palo Alto, CA, USA.
5
Program for Evolutionary Dynamics, Harvard University, Cambridge, MA, USA.
6
The Ludwig Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
7
VU University Amsterdam, Master's Oncology Program, VU University Medical Center, Amsterdam, The Netherlands.
8
Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan.
9
Department of Art as Applied to Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
10
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
11
Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
12
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
13
Department of Mathematics, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA.
14
Howard Hughes Medical Institute, The Johns Hopkins Kimmel Cancer Center, Baltimore, MD, USA.
15
The David M. Rubenstein Center for Pancreatic Cancer Research, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. iacobuzc@mskcc.org.
16
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. iacobuzc@mskcc.org.

Abstract

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.

PMID:
30177826
DOI:
10.1038/s41586-018-0481-8

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