GENETIC ALTERATIONS IN GASTRINOMAS AND NONFUNCTIONING PANCREATIC NEUROENDOCRINE TUMORS - AN ANALYSIS OF P16 MTS1 TUMOR-SUPPRESSOR GENE INACTIVATION/

Neoplasms of the endocrine pancreas are extremely rare, and molecular mechanisms influencing their development are poorly understood. Nevert heless, 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 exami ned for mutations and homozygous deletions using ''Cold'' single-stran d conformation polymorphism and semiquantitative PCR-based analyses, r espectively. Samples were also analyzed for the presence of 5' CpG isl and hypermethylation using methylation-specific PCR. The p16/MTS1 gene was found to be homozygously deleted in 41.7% of tumors and methylate d in 58.3%, but no mutations were identified by single-strand conforma tion polymorphism analyses. Overall, 91.7% of the specimens demonstrat ed inactivating alterations in p16/MTS1. These data suggest that trans criptional silencing of p16/MTS1 is a frequent event in these rare and poorly understood tumors.