Multiple genes are hypermethylated in intraductal papillary mucinous neoplasms of the pancreas

Seung Mo Hong, David Kelly, Margaret Griffith, Noriyuki Omura, Ang Li, Chung Pin Li, Ralph H Hruban, Michael S Goggins

Research output: Contribution to journalArticle

Abstract

Ductal adenocarcinoma of the pancreas is the fourth leading cause of cancer death and is usually diagnosed late. Intraductal papillary mucinous neoplasms are an increasingly recognized precursor to invasive ductal adenocarcinoma of the pancreas. Identifying the alterations in DNA methylation that arise during intraductal papillary mucinous neoplasm development may facilitate the development of markers that could be used to differentiate intraductal papillary mucinous neoplasms from non-neoplastic pancreatic cystic lesions. Surgically resected intraductal papillary mucinous neoplasms and adjacent ductal adenocarcinomas were microdissected from 50 patients. Normal pancreas was also obtained from 27 patients with intraductal papillary mucinous neoplasms or pancreatic adenocarcinomas and 10 patients with well-differentiated pancreatic endocrine neoplasms. Methylation-specific PCR was performed on isolated DNA for seven genes (SPARC, SARP2, TSLC1, RELN, TFPI2, CLDN5, UCHL1) known to be commonly aberrantly methylated in pancreatic ductal adenocarcinomas. The mean percentage of genes methylated in invasive ductal adenocarcinomas arising in association with an intraductal papillary mucinous neoplasm (mean±s.d., 81±17%) was significantly higher than that in noninvasive-intraductal papillary mucinous neoplasms (57±26%, P=0.007) or peritumoral normal epithelial cells (22±17%, P

Original languageEnglish (US)
Pages (from-to)1499-1507
Number of pages9
JournalModern Pathology
Volume21
Issue number12
DOIs
StatePublished - Dec 2008

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Keywords

  • DNA methylation
  • Intraductal papillary mucinous neoplasm
  • Pancreatic cancer
  • Pancreatic endocrine neoplasm
  • SPARC

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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