Genetic alterations in gastrinomas and nonfunctioning pancreatic neuroendocrine tumors: an analysis of p16/MTS1 tumor suppressor gene inactivation

Cancer Res. 1998 Jan 15;58(2):237-40.


Neoplasms of the endocrine pancreas are extremely rare, and molecular mechanisms influencing their development are poorly understood. Nevertheless, gastrinomas have become a paradigm for the study of hormonally active tumors. In the present study, 12 gastrinoma and nonfunctioning pancreatic neuroendocrine tumor specimens were evaluated for genetic alterations of the p16/MTS1 tumor suppressor gene. DNA extracted from microdissected portions of paraffin-embedded tumor sections were examined for mutations and homozygous deletions using "Cold" single-strand conformation polymorphism and semiquantitative PCR-based analyses, respectively. Samples were also analyzed for the presence of 5' CpG island hypermethylation using methylation-specific PCR. The p16/MTS1 gene was found to be homozygously deleted in 41.7% of tumors and methylated in 58.3%, but no mutations were identified by single-strand conformation polymorphism analyses. Overall, 91.7% of the specimens demonstrated inactivating alterations in p16/MTS1. These data suggest that transcriptional silencing of p16/MTS1 is a frequent event in these rare and poorly understood tumors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • CpG Islands
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • DNA Methylation
  • DNA Primers / chemistry
  • DNA, Neoplasm / analysis
  • Gastrinoma / genetics*
  • Gastrinoma / metabolism
  • Gastrinoma / pathology
  • Gene Deletion*
  • Genes, p16 / genetics*
  • Humans
  • Neuroendocrine Tumors / genetics*
  • Neuroendocrine Tumors / metabolism
  • Neuroendocrine Tumors / pathology
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Point Mutation*
  • Polymerase Chain Reaction


  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA Primers
  • DNA, Neoplasm