Deletions of RDINK4/ARF enhancer in gastrinomas and nonfunctioning pancreatic neuroendocrine tumors

Ming J. Poi, Joe Drosdeck, Wendy L. Frankel, Peter Muscarella, Junan Li

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Objective: The presence of an enhancer element, RDINK4/ARF (RD), in the prominent INK4-ARF locus provides a novel en bloc mechanism to simultaneously regulate the transcription of p15, p14ARF, and p16 genes. However, knowledge about RD alterations and its potential contributions to cancer progression remains limited. In this study, we aimed to evaluate the incidence of RD alterations in pancreatic tumors.

Methods: DNAs from 14 gastrinomas and 6 nonfunctioning pancreatic neuroendocrine tumors were subjected to quantitative real-time polymerase chain reaction-based assays to determine deletions in p15, p14ARF, and p16 (both exons 1 and 2).

Results: RDINK4/ARF was frequently deleted in gastrinomas and nonfunctioning pancreatic neuroendocrine tumors with an incidence of 30% (6/20 samples). In comparison, the incidences of deletions of p15 (exon 1), p14ARF (exon 1β), and p16 (exon 1α) are 10% (2/20 samples), 10% (2/20 samples), and 45% (9/20 samples), respectively. Whereas some RD deletion events arose from deletions of the entire INK4-ARF locus, RD deletions in some specimens seemed to be independent of genetic alterations in any of the p15, p14ARF, and p16 genes.

Conclusions: Our results strongly support that the deletion of RD may represent a novel mechanism to simultaneously downregulate p15, p14ARF, and p16, thus contributing to the development of human pancreatic cancers.

Original languageEnglish (US)
Pages (from-to)1009-1013
Number of pages5
JournalPancreas
Volume43
Issue number7
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Keywords

  • Gastrinomas
  • Gene deletion
  • Nonfunctioning pancreatic neuroendocrine tumor
  • RD
  • The INK4-ARF locus

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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