Precancerous neoplastic cells can move through the pancreatic ductal system

Alvin P. Makohon-Moore, Karen Matsukuma, Ming Zhang, Johannes G. Reiter, Jeffrey M. Gerold, Yuchen Jiao, Lisa Sikkema, Marc A. Attiyeh, Shinichi Yachida, Corinne Sandone, Ralph H. Hruban, David S. Klimstra, Nickolas Papadopoulos, Martin A. Nowak, Kenneth W. Kinzler, Bert Vogelstein and Christine A. Iacobuzio-Donahue ()
Additional contact information
Alvin P. Makohon-Moore: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
Karen Matsukuma: University of California, Davis
Ming Zhang: The Johns Hopkins University School of Medicine
Johannes G. Reiter: Stanford University School of Medicine
Jeffrey M. Gerold: Harvard University
Yuchen Jiao: The Johns Hopkins University School of Medicine
Lisa Sikkema: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
Marc A. Attiyeh: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
Shinichi Yachida: Graduate School of Medicine, Osaka University
Corinne Sandone: The Johns Hopkins University School of Medicine
Ralph H. Hruban: The Johns Hopkins University School of Medicine
David S. Klimstra: Memorial Sloan Kettering Cancer Center
Nickolas Papadopoulos: The Johns Hopkins University School of Medicine
Martin A. Nowak: Harvard University
Kenneth W. Kinzler: The Johns Hopkins University School of Medicine
Bert Vogelstein: The Johns Hopkins University School of Medicine
Christine A. Iacobuzio-Donahue: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center

Nature, 2018, vol. 561, issue 7722, 201-205

Abstract: 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.

Keywords: Driver Genes; Driver Gene Mutations; Noninvasive Precursor Lesions; Pancreatic Intraepithelial Neoplasia (PanIN); Pancreatic Ductal Adenocarcinoma (PDAC) (search for similar items in EconPapers)
Date: 2018
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DOI: 10.1038/s41586-018-0481-8

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