From somatic mutation to early detection: insights from molecular characterization of pancreatic cancer precursor lesions

J Pathol. 2018 Dec;246(4):395-404. doi: 10.1002/path.5154.

Abstract

Pancreatic cancer arises from noninvasive precursor lesions, including pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm (IPMN), and mucinous cystic neoplasm (MCN), which are curable if detected early enough. Recently, these types of precursor lesions have been extensively characterized at the molecular level, defining the timing of critical genetic alterations in tumorigenesis pathways. The results of these studies deepen our understanding of tumorigenesis in the pancreas, providing novel insights into tumor initiation and progression. Perhaps more importantly, they also provide a rational foundation for early detection approaches that could allow clinical intervention prior to malignant transformation. In this review, we summarize the results of comprehensive molecular characterization of PanINs, IPMNs, and MCNs and discuss the implications for cancer biology as well as early detection. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Keywords: cancer genomics; driver gene; intraductal papillary mucinous neoplasm; mucinous cystic neoplasm; pancreatic cancer precursor lesion; pancreatic intraepithelial neoplasia; somatic mutation.

Publication types

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

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Carcinoma in Situ / genetics*
  • Carcinoma in Situ / metabolism
  • Carcinoma in Situ / pathology
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Early Detection of Cancer / methods
  • Genetic Heterogeneity
  • Genetic Predisposition to Disease
  • Humans
  • Molecular Diagnostic Techniques
  • Mutation / genetics*
  • Neoplasms, Cystic, Mucinous, and Serous / genetics*
  • Neoplasms, Cystic, Mucinous, and Serous / metabolism
  • Neoplasms, Cystic, Mucinous, and Serous / pathology
  • Pancreatic Intraductal Neoplasms / genetics*
  • Pancreatic Intraductal Neoplasms / metabolism
  • Pancreatic Intraductal Neoplasms / pathology
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Phenotype
  • Precancerous Conditions / genetics*
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / pathology
  • Risk Factors

Substances

  • Biomarkers, Tumor