PMID- 22925896 OWN - NLM STAT- MEDLINE DCOM- 20130207 LR - 20121002 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 426 IP - 3 DP - 2012 Sep 28 TI - WT1 CpG islands methylation in human lung cancer: a pilot study. PG - 306-9 LID - S0006-291X(12)01569-0 [pii] LID - 10.1016/j.bbrc.2012.08.059 [doi] AB - BACKGROUND: CpG island hypermethylation of gene promoters and regulatory regions is a well-known mechanism of epigenetic silencing of tumor suppressors and is directly linked to carcinogenesis. Wilm's tumor gene (WT1) is a tumor suppressor protein involved in the regulation of human cell growth and differentiation and a modulator of oncogenic K Ras signaling in lung cancer. Changes in the pattern of methylation of the WT1 gene have not yet been studied in detail in human lung cancer. In this study we compared the methylation profile of WT1 gene in samples of neoplastic and non-neoplastic lung tissue taken from the same patients. METHODS: DNA was extracted from neoplastic and normal lung tissue obtained from 16 patients with non small cell lung cancer (NSCLC). The methylation status of 29 CpG islands in the 5' region of WT1 was determined by pyrosequencing. Statistical analysis was carried out by T test and Mann Whitney test. RESULTS: The mean percentage of methylation, considering all CpG islands of WT1 in the neoplastic tissues of the 16 NSCLC patients, was 16.2 +/- 3.4, whereas in the normal lung tissue from the same patients it was 5.6 +/- 1.7 (p < 0.001). Adenocarcinomas presented higher methylation levels than squamous cell carcinomas (p < 0,001). CONCLUSIONS: Methylation of WT1 gene is significantly increased in NSCLC. Both histotype and exposure to cigarette smoke heavily influence the pattern of CpG islands which undergo hypermethylation. CI - Copyright (c) 2012 Elsevier Inc. All rights reserved. FAU - Bruno, Pierdonato AU - Bruno P AD - Department of Clinic and Molecular Medicine, Sapienza University of Rome, Italy. FAU - Gentile, Giovanna AU - Gentile G FAU - Mancini, Rita AU - Mancini R FAU - De Vitis, Claudia AU - De Vitis C FAU - Esposito, Maria Cristina AU - Esposito MC FAU - Scozzi, Davide AU - Scozzi D FAU - Mastrangelo, Mario AU - Mastrangelo M FAU - Ricci, Alberto AU - Ricci A FAU - Mohsen, Ibrahim AU - Mohsen I FAU - Ciliberto, Gennaro AU - Ciliberto G FAU - Simmaco, Maurizio AU - Simmaco M FAU - Mariotta, Salvatore AU - Mariotta S LA - eng PT - Journal Article DEP - 20120820 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (WT1 Proteins) SB - IM MH - Adenocarcinoma/genetics/pathology MH - Aged MH - Carcinoma, Non-Small-Cell Lung/*genetics/pathology MH - Cell Transformation, Neoplastic/genetics MH - *CpG Islands MH - *DNA Methylation MH - *Gene Expression Regulation, Neoplastic MH - *Gene Silencing MH - Humans MH - Lung/metabolism/pathology MH - Lung Neoplasms/*genetics/pathology MH - Male MH - Middle Aged MH - Pilot Projects MH - Smoking/genetics MH - WT1 Proteins/*genetics EDAT- 2012/08/29 06:00 MHDA- 2013/02/08 06:00 CRDT- 2012/08/29 06:00 PHST- 2012/08/03 00:00 [received] PHST- 2012/08/13 00:00 [accepted] PHST- 2012/08/29 06:00 [entrez] PHST- 2012/08/29 06:00 [pubmed] PHST- 2013/02/08 06:00 [medline] AID - S0006-291X(12)01569-0 [pii] AID - 10.1016/j.bbrc.2012.08.059 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2012 Sep 28;426(3):306-9. doi: 10.1016/j.bbrc.2012.08.059. Epub 2012 Aug 20.