@article{34cfcb929773469394851583af0045b6,
title = "Aberrant methylation of the 5′ CpG island of TSLC1 is common in pancreatic ductal adenocarcinoma and is first manifest in high-grade PanINs",
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.",
keywords = "CpG island, Methylation, PanIN, Pancreatic adenocarcinoma, TSLC1",
author = "Marnix Jansen and Noriyoshi Fukushima and Christophe Rosty and Kim Walter and Renee Altink and {Van Heek}, Tjarda and Ralph Hruban and Offerhaus, {Johan G.} and Michael Goggins",
note = "Funding Information: Mounting evidence indicates the involvement of 5{\textquoteright} CpG island methylation in the silencing of tumor-suppressor genes.1-3 A novel tumor-suppressor gene termed TSLC1 for tumor-suppressor in lung cancer-1 (also known as Igsf4) was recently identified using a combination of loss of heterozygosity (LOH) and functional complementation studies.4 In this study, truncating mutations of TSLC1 with LOH were identified in 1 of 66 non-small cell lung carcinomas (NSCLC) and in 1 of 44 hepatocellular carcinomas. TSLC1 is predicted to encode for a putative transmembrane glycoprotein of 442 amino acids and is ubiquitously expressed in multiple tissue types including the pancreas. The protein carries a structural homology to cell adhesion molecules NCAM1 and NCAM2 indicating that it might be involved in intercellular and/ or interactions with the extracel-lular matrix (ECM). Recently, two novel genes homologous to TSLC1, termed TSLL1 and Supported by The NIH SPORE grant in gastrointestinal malignancies (CA62924), the TSLL2, were identified.5 Loss of expression of these genes in gliomas and in prostate research and the Koningin Wilhelmina Foundation for cancer prevention.Lustgarten Foundation and the Michael Rolfe Foundation for pancreatic cancer carcinomas was recently reported indicating that TSLC1 is part of superfamily of immunoglobulin genes exhibiting loss of expression in multiple cancer types.",
year = "2002",
doi = "10.4161/cbt.84",
language = "English (US)",
volume = "1",
pages = "293--296",
journal = "Cancer Biology and Therapy",
issn = "1538-4047",
publisher = "Landes Bioscience",
number = "3",
}