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. 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.
Muscarella
P
P
Division of General Surgery, College of Medicine and Public Health, The Ohio State University, Columbus 43210-1240, USA.
Melvin
W S
WS
Fisher
W E
WE
Foor
J
J
Ellison
E C
EC
Herman
J G
JG
Schirmer
W J
WJ
Hitchcock
C L
CL
DeYoung
B R
BR
Weghorst
C M
CM
D018899:CpG Islands; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D015408:Gastrinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D019942:Genes, p16 / Q000235:genetics*; D006801:Humans; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017354:Point Mutation; D016133:Polymerase Chain Reaction
D019941:Cyclin-Dependent Kinase Inhibitor p16; D017931:DNA Primers; D004273:DNA, Neoplasm