Genetics of Familial and Sporadic Pancreatic Cancer

Gastroenterology. 2019 May;156(7):2041-2055. doi: 10.1053/j.gastro.2018.12.039. Epub 2019 Jan 18.

Abstract

In the previous decade, comprehensive genomic analyses have yielded important insights about the genetic alterations that underlie pancreatic tumorigenesis. Whole-exome and whole-genome sequencing of pancreatic ductal adenocarcinomas have confirmed the critical driver genes altered in the majority of pancreatic cancers, as well as identified numerous less frequently altered driver genes, and have delineated cancer subgroups with unique biological and clinical features. It is now appreciated that pancreatic susceptibility gene alterations are often identified in patients with pancreatic cancer without family histories suggestive of a familial cancer syndrome, prompting recent efforts to expand gene testing to all patients with pancreatic cancer. Studies of pancreatic cancer precursor lesions have begun to elucidate the evolutionary history of pancreatic tumorigenesis and to help us understand the utility of biomarkers for early detection and targets to develop new therapeutic strategies. In this review, we discuss the results of comprehensive genomic characterization of pancreatic ductal adenocarcinoma and its precursor lesions, and we highlight translational applications in early detection and therapy.

Keywords: Gene Testing; Mutation; Pancreatic Cancer; Progression Model.

Publication types

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

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / pathology
  • Carcinoma, Pancreatic Ductal / therapy
  • Clinical Decision-Making
  • Early Detection of Cancer / methods*
  • Genetic Predisposition to Disease
  • Genetic Testing*
  • Genetic Variation*
  • Heredity
  • Humans
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy
  • Pedigree
  • Phenotype
  • Precision Medicine
  • Predictive Value of Tests
  • Risk Assessment
  • Risk Factors

Substances

  • Biomarkers, Tumor