Precancerous neoplastic cells can move through the pancreatic ductal system,Nature

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Precancerous neoplastic cells can move through the pancreatic ductal system
Nature ( IF 50.5 ) Pub Date : 2018-09-01 , DOI: 10.1038/s41586-018-0481-8
Alvin P Makohon-Moore ₁ , Karen Matsukuma ₂ , Ming Zhang ₃ , Johannes G Reiter _{4,

5} , Jeffrey M Gerold ₅ , Yuchen Jiao ₆ , Lisa Sikkema _{1,

7} , Marc A Attiyeh ₁ , Shinichi Yachida ₈ , Corinne Sandone ₉ , Ralph H Hruban _{3,

10,

11} , David S Klimstra ₁₂ , Nickolas Papadopoulos ₆ , Martin A Nowak _{5,

13} , Kenneth W Kinzler ₆ , Bert Vogelstein _{3,

6,

14} , Christine A Iacobuzio-Donahue _{1,

12}

Affiliation

The David M. Rubenstein Center for Pancreatic Cancer Research, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Pathology, University of California, Davis, Sacramento, CA, USA.
The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Canary Center for Cancer Early Detection, Department of Radiology, Stanford University School of Medicine, Palo Alto, CA, USA.
Program for Evolutionary Dynamics, Harvard University, Cambridge, MA, USA.
The Ludwig Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
VU University Amsterdam, Master's Oncology Program, VU University Medical Center, Amsterdam, The Netherlands.
Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan.
Department of Art as Applied to Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Mathematics, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA.
Howard Hughes Medical Institute, The Johns Hopkins Kimmel Cancer Center, Baltimore, MD, USA.

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.Comparison of multiple lesions from individual pancreases sheds light on how ancestral clones can spread through the ductal system and give rise to precursor lesions, with acquisition of further mutations leading to pancreatic cancer.

中文翻译：

癌前肿瘤细胞可以通过胰腺导管系统

大多数成人癌是从非侵入性前体病变发展而来的，遗传分析支持这一进展。然而，共存病变之间的进化和遗传关系尚不清楚。在这里，我们分析了从同一胰腺不同区域取样的胰腺癌的体细胞变异和前体病变。在推断出进化关系后，我们发现祖先细胞已经开始并克隆性扩展形成一个或多个病变，随后的驱动基因突变最终导致侵袭性胰腺癌。我们估计，这种多步进展通常跨越多年。这些新数据通过说明独立的、

更新日期：2018-09-01

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