Genetic alterations in gastrinomas and nonfunctioning pancreatic neuroendocrine tumors

An analysis of p16/MTS1 tumor suppressor gene inactivation

Peter Muscarella, W. Scott Melvin, William E. Fisher, John Foor, E. Christopher Ellison, James G. Herman, William J. Schirmer, Charles L. Hitchcock, Barry R. DeYoung, Christopher M. Weghorst

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

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 non-functioning 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.

Original languageEnglish (US)
Pages (from-to)237-240
Number of pages4
JournalCancer Research
Volume58
Issue number2
StatePublished - Jan 15 1998
Externally publishedYes

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Gastrinoma
Neuroendocrine Tumors
Gene Silencing
Tumor Suppressor Genes
p16 Genes
Neoplasms
Polymerase Chain Reaction
CpG Islands
Sequence Deletion
Islets of Langerhans
Paraffin
Methylation
Mutation
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Genetic alterations in gastrinomas and nonfunctioning pancreatic neuroendocrine tumors : An analysis of p16/MTS1 tumor suppressor gene inactivation. / Muscarella, Peter; Melvin, W. Scott; Fisher, William E.; Foor, John; Ellison, E. Christopher; Herman, James G.; Schirmer, William J.; Hitchcock, Charles L.; DeYoung, Barry R.; Weghorst, Christopher M.

In: Cancer Research, Vol. 58, No. 2, 15.01.1998, p. 237-240.

Research output: Contribution to journalArticle

Muscarella, P, Melvin, WS, Fisher, WE, Foor, J, Ellison, EC, Herman, JG, Schirmer, WJ, Hitchcock, CL, DeYoung, BR & Weghorst, CM 1998, 'Genetic alterations in gastrinomas and nonfunctioning pancreatic neuroendocrine tumors: An analysis of p16/MTS1 tumor suppressor gene inactivation', Cancer Research, vol. 58, no. 2, pp. 237-240.
Muscarella, Peter ; Melvin, W. Scott ; Fisher, William E. ; Foor, John ; Ellison, E. Christopher ; Herman, James G. ; Schirmer, William J. ; Hitchcock, Charles L. ; DeYoung, Barry R. ; Weghorst, Christopher M. / Genetic alterations in gastrinomas and nonfunctioning pancreatic neuroendocrine tumors : An analysis of p16/MTS1 tumor suppressor gene inactivation. In: Cancer Research. 1998 ; Vol. 58, No. 2. pp. 237-240.
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