Aberrant methylation of the 5′ CpG island of TSLC1 is common in pancreatic ductal adenocarcinoma and is first manifest in high-grade PanINs

Marnix Jansen, Noriyoshi Fukushima, Christophe Rosty, Kim Walter, Renee Altink, Tjarda Van Heek, Ralph Hruban, Johan G. Offerhaus, Michael Goggins

Research output: Contribution to journalArticle

Abstract

The recently identified tumor-suppressor gene TSLC1 on chromosome 11q23.2 is frequently inactivated in human non-small cell lung adenocarcinoma by DNA methylation-associated silencing. The aim of this study was to determine if TSLC1 is inactivated in adenocarcinoma of the pancreas. We analyzed 17 pancreatic cancer cell lines, 91 primary pancreatic adenocarcinoma, 46 pancreatic intraepithelial (PanIN) precursor lesions and 15 microscopically normal pancreata for methylation of the 5′ CpG island of the TSLC1 gene through methylation-specific PCR. We observed 5′ CpG methylation of TSLC1 in 4 of 17 cell lines (24%). In each cell line the aberrant methylation was associated with loss of TSLC1 expression by RT-PCR that was reversible after treatment with the DNA methyltransferase inhibitor 5-aza-2′- deoxycytidine. Furthermore, we observed that TSLC1 was methylated in 25 of 91 primary pancreatic adenocarcinomas (27%), and in 2 of 7 highgrade PanIN-3 lesions (29%), but not in low-grade PanIN (0 of 9 PanIN-2 and 0 of 30 PanIN-1) lesions or in normal pancreata (n=15). We conclude that epigenetic silencing of TSLC1 expression through 5′ CpG island associated methylation is common in pancreatic adenocarcinoma and is a late event in pancreatic neoplastic development.

Original languageEnglish (US)
Pages (from-to)293-296
Number of pages4
JournalCancer Biology and Therapy
Volume1
Issue number3
DOIs
StatePublished - Jan 1 2002

Keywords

  • CpG island
  • Methylation
  • PanIN
  • Pancreatic adenocarcinoma
  • TSLC1

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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