title: Deletions of RDINK4/ARF enhancer in gastrinomas and nonfunctioning pancreatic neuroendocrine tumors.
abstract: OBJECTIVE
  The presence of an enhancer element, RD (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
  RD 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.
authors.affiliation: From the *Department of Pharmacy, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, †College of Pharmacy, ‡Comprehensive Cancer Center, Departments of §Surgery and ∥Pathology, College of Medicine, and ¶Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, OH.
authors.forename: Ming J
authors.initials: MJ
authors.lastname: Poi
authors.forename: Joe
authors.initials: J
authors.lastname: Drosdeck
authors.forename: Wendy L
authors.initials: WL
authors.lastname: Frankel
authors.forename: Peter
authors.initials: P
authors.lastname: Muscarella
authors.forename: Junan
authors.initials: J
authors.lastname: Li
mesh_terms: D015331:Cohort Studies; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D018450:Disease Progression; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005091:Exons / Q000235:genetics; D015408:Gastrinoma / Q000235:genetics* / Q000503:physiopathology; D017353:Gene Deletion; D019942:Genes, p16 / Q000502:physiology; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000503:physiopathology; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000503:physiopathology; D060888:Real-Time Polymerase Chain Reaction; D017384:Sequence Deletion; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics
chemical_list: D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D025803:Tumor Suppressor Protein p14ARF