title: WT1 CpG islands methylation in human lung cancer: a pilot study.
abstract: 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.
authors.affiliation: Department of Clinic and Molecular Medicine, Sapienza University of Rome, Italy.
authors.forename: Pierdonato
authors.initials: P
authors.lastname: Bruno
authors.forename: Giovanna
authors.initials: G
authors.lastname: Gentile
authors.forename: Rita
authors.initials: R
authors.lastname: Mancini
authors.forename: Claudia
authors.initials: C
authors.lastname: De Vitis
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Esposito
authors.forename: Davide
authors.initials: D
authors.lastname: Scozzi
authors.forename: Mario
authors.initials: M
authors.lastname: Mastrangelo
authors.forename: Alberto
authors.initials: A
authors.lastname: Ricci
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Mohsen
authors.forename: Gennaro
authors.initials: G
authors.lastname: Ciliberto
authors.forename: Maurizio
authors.initials: M
authors.lastname: Simmaco
authors.forename: Salvatore
authors.initials: S
authors.lastname: Mariotta
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D018899:CpG Islands; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012907:Smoking / Q000235:genetics; D025721:WT1 Proteins / Q000235:genetics*
chemical_list: D025721:WT1 Proteins