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

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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.

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

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

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title = "Precancerous neoplastic cells can move through the pancreatic ductal system",

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.",

author = "Makohon-Moore, {Alvin P.} and Karen Matsukuma and Ming Zhang and Reiter, {Johannes G.} and Gerold, {Jeffrey M.} and Yuchen Jiao and Lisa Sikkema and Attiyeh, {Marc A.} and Shinichi Yachida and Corinne Sandone and Hruban, {Ralph H.} and Klimstra, {David S.} and Nickolas Papadopoulos and Nowak, {Martin A.} and Kinzler, {Kenneth W.} and Bert Vogelstein and Iacobuzio-Donahue, {Christine A.}",

note = "Funding Information: Acknowledgements Supported by the V Foundation for Cancer Research, NIH grants F31 CA180682, 2T32 CA160001-06 and 5T32 CA067751-13, an Erwin Schr{\"o}dinger fellowship (Austrian Science Fund FWF J-3996), SPORE grant P50 CA062924, the Michael Rolfe Foundation, The Lustgarten Foundation for Cancer Research, the Sol Goldman Center for Pancreatic Cancer Research, The Virginia and D.K. Ludwig Fund for Cancer Research and D. Troper and S. Wojcicki. Publisher Copyright: {\textcopyright} 2018, Springer Nature Limited.",

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AU - Matsukuma, Karen

AU - Zhang, Ming

AU - Reiter, Johannes G.

AU - Gerold, Jeffrey M.

AU - Jiao, Yuchen

AU - Sikkema, Lisa

AU - Attiyeh, Marc A.

AU - Yachida, Shinichi

AU - Sandone, Corinne

AU - Hruban, Ralph H.

AU - Klimstra, David S.

AU - Papadopoulos, Nickolas

AU - Nowak, Martin A.

AU - Kinzler, Kenneth W.

AU - Vogelstein, Bert

AU - Iacobuzio-Donahue, Christine A.

N1 - Funding Information: Acknowledgements Supported by the V Foundation for Cancer Research, NIH grants F31 CA180682, 2T32 CA160001-06 and 5T32 CA067751-13, an Erwin Schrödinger fellowship (Austrian Science Fund FWF J-3996), SPORE grant P50 CA062924, the Michael Rolfe Foundation, The Lustgarten Foundation for Cancer Research, the Sol Goldman Center for Pancreatic Cancer Research, The Virginia and D.K. Ludwig Fund for Cancer Research and D. Troper and S. Wojcicki. Publisher Copyright: © 2018, Springer Nature Limited.

PY - 2018/9/13

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N2 - 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.

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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Precancerous neoplastic cells can move through the pancreatic ductal system

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