Precancerous neoplastic cells can move through the pancreatic ductal system

Nature. 2018 Sep;561(7722):201-205. doi: 10.1038/s41586-018-0481-8. Epub 2018 Sep 3.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Lineage / genetics
  • Disease Progression
  • Evolution, Molecular
  • Humans
  • INDEL Mutation / genetics
  • Models, Biological
  • Mutagenesis
  • Neoplasm Invasiveness
  • Pancreatic Ducts / metabolism
  • Pancreatic Ducts / pathology*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology
  • Polymorphism, Single Nucleotide / genetics
  • Precancerous Conditions / genetics
  • Precancerous Conditions / pathology*
  • Time Factors
  • Whole Exome Sequencing