title: p16 gene alterations in human ovarian cancers: comparison between tissue and blood samples.
abstract: OBJECTIVE
  To determine the alterations of tumor suppressor gene p16INK4A in human ovarian cancers to explore the possibilities of identifying potential minimally invasive markers in blood of the patients, which could help in the clinical practice as a diagnostic and prognostic marker.
  
  
  METHODS
  Ovarian cancer tissue and corresponding blood samples were collected from patients (n = 50). The promoter methylation and mutation status of p16 gene in blood and ovarian tissue DNA was then assessed using methylation-specific polymerase chain reaction and denaturing high-performance liquid chromatography along with DNA sequencing method. In addition, the protein expression in ovarian cancer tissue samples was detected by immunostaining method using monoclonal antibodies against p16.
  
  
  RESULTS
  Methylation of p16 was observed in 56% (28/50) of the cases. The data showed concordance in promoter methylation status of p16 gene between the tumor tissue and the corresponding blood DNA samples of the patients with ovarian cancer. There was a weak statistical agreement (Kendall tau b = +0.31), and a perfect correspondence was observed in 50% of the cases. The p16 mutations were comparatively low, revealing only 2 variations among the samples analyzed. The percentage of protein expression was inversely correlated with the p16 gene promoter methylation.
  
  
  CONCLUSIONS
  This study demonstrates that the p16 gene plays a role in the progression of human ovarian cancers and the blood DNA methylation of p16 gene promoter region is a weak predictor of tumor tissue methylation status.
authors.affiliation: Human Genetics Laboratory, Department of Zoology, Osmania University, Hyderabad, India. soujanya27@gmail.com
authors.forename: Lakshmi Sowjanya
authors.initials: LS
authors.lastname: Bammidi
authors.forename: Geetha Nagasree
authors.initials: GN
authors.lastname: Neerukonda
authors.forename: Sudha
authors.initials: S
authors.lastname: Murthy
authors.forename: Rudrama Devi
authors.initials: RD
authors.lastname: Kanapuram
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000097:blood / Q000235:genetics*; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D055815:Young Adult
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins