TY - JOUR
T1 - Precancerous neoplastic cells can move through the pancreatic ductal system
AU - Makohon-Moore, Alvin P.
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.
PY - 2018/9/13
Y1 - 2018/9/13
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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U2 - 10.1038/s41586-018-0481-8
DO - 10.1038/s41586-018-0481-8
M3 - Article
C2 - 30177826
AN - SCOPUS:85053232388
VL - 561
SP - 201
EP - 205
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7722
ER -