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

Jansen, M., Fukushima, N., Rosty, C., Walter, K., Altink, R., van Heek, T., Hruban, R., Offerhaus, J. G. and Goggins, M. (2002) Aberrant methylation of the 5 ' CpG island of TSLC1 is common in pancreatic ductal adenocarcinoma and is first manifest in high-grade PanINs. Cancer Biology and Therapy, 1 3: 293-296.

Author Jansen, M.
Fukushima, N.
Rosty, C.
Walter, K.
Altink, R.
van Heek, T.
Hruban, R.
Offerhaus, J. G.
Goggins, M.
Title Aberrant methylation of the 5 ' CpG island of TSLC1 is common in pancreatic ductal adenocarcinoma and is first manifest in high-grade PanINs
Journal name Cancer Biology and Therapy   Check publisher's open access policy
ISSN 1538-4047
1555-8576
Publication date 2002-05
Sub-type Article (original research)
Volume 1
Issue 3
Start page 293
End page 296
Total pages 4
Place of publication Austin, TX, United States
Publisher Landes Bioscience
Language eng
Formatted 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.
Keyword Tslc1
CpG island
Methylation
Pancreatic adenocarcinoma
PanIN
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Wed, 09 Mar 2011, 14:20:55 EST