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; Christine A. Iacobuzio-Donahue

doi:10.1038/s41586-018-0481-8

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, Christine A. Iacobuzio-Donahue

School of Medicine

Research output: Contribution to journal › Article

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.

Original language	English (US)
Pages (from-to)	201-205
Number of pages	5
Journal	Nature
Volume	561
Issue number	7722
DOIs	https://doi.org/10.1038/s41586-018-0481-8
State	Published - Sep 13 2018

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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. (2018). Precancerous neoplastic cells can move through the pancreatic ductal system. Nature, 561(7722), 201-205. https://doi.org/10.1038/s41586-018-0481-8

Precancerous neoplastic cells can move through the pancreatic ductal system. / Makohon-Moore, Alvin P.; Matsukuma, Karen; Zhang, Ming; Reiter, Johannes G.; Gerold, Jeffrey M.; Jiao, Yuchen; Sikkema, Lisa; Attiyeh, Marc A.; Yachida, Shinichi; Sandone, Corinne ; Hruban, Ralph H; Klimstra, David S.; Papadopoulos, Nickolas; Nowak, Martin A.; Kinzler, Kenneth W ; Vogelstein, Bert; Iacobuzio-Donahue, Christine A.

In: Nature, Vol. 561, No. 7722, 13.09.2018, p. 201-205.

Research output: Contribution to journal › Article

Makohon-Moore, AP, Matsukuma, K, Zhang, M, Reiter, JG, Gerold, JM, Jiao, Y, Sikkema, L, Attiyeh, MA, Yachida, S, Sandone, C , Hruban, RH, Klimstra, DS, Papadopoulos, N, Nowak, MA, Kinzler, KW , Vogelstein, B & Iacobuzio-Donahue, CA 2018, 'Precancerous neoplastic cells can move through the pancreatic ductal system', Nature, vol. 561, no. 7722, pp. 201-205. https://doi.org/10.1038/s41586-018-0481-8

Makohon-Moore, Alvin P. ; Matsukuma, Karen ; Zhang, Ming ; Reiter, Johannes G. ; Gerold, Jeffrey M. ; Jiao, Yuchen ; Sikkema, Lisa ; Attiyeh, Marc A. ; Yachida, Shinichi ; Sandone, Corinne ; Hruban, Ralph H ; Klimstra, David S. ; Papadopoulos, Nickolas ; Nowak, Martin A. ; Kinzler, Kenneth W ; Vogelstein, Bert ; Iacobuzio-Donahue, Christine A. / Precancerous neoplastic cells can move through the pancreatic ductal system. In: Nature. 2018 ; Vol. 561, No. 7722. pp. 201-205.

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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.",

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AU - Hruban, Ralph H

AU - Klimstra, David S.

AU - Papadopoulos, Nickolas

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AB - 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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