title: Status of p16(INK4a) and E-cadherin gene promoter methylation in Moroccan patients with cervical carcinoma.
abstract: Aberrant methylation of tumor suppressor gene promoters has been extensively investigated in cervical cancer. Transcriptional silencing, as a main consequence of hypermethylation of CpG islands, is the predominant mechanism of p16(INK4a) and E-cadherin gene inactivation in malignant epithelial tumors. This study was conducted to evaluate the promoter methylation status of p16(INK4a) and E-cadherin genes in 22 specimens of cervical carcinomas, four cervical cancer cell lines (HeLa, SiHa, Caski, C33A), and 20 human papillomavirus negative specimens, obtained from normal cervical swabs, using the methylation-specific PCR approach. Hypermethylation of the 5' CpG island of the p16(INK4a) and E-cadherin genes were found in 13 (59.1%) and 10 (45.5%) of 22 cervical cancer samples, respectively. Furthermore, our findings did not show any correlation between promoter methylation of p16(INK4a) and E-cadherin genes and clinicopathological parameters, including HPV infection, phenotypic distribution, and stage of the disease. However, hypermethylation of E-cadherin gene promoter appears to be age related in cervical cancer, whereas the frequency of aberrant methylation of p16(INK4a) gene promoter is unchanged according to the age of patients. Thus, caution must be made to use these markers in the diagnosis of cervical cancer. However, dietary or pharmaceutical agents that can inhibit these epigenetic events may prevent or delay the development of cervical cancer.
authors.affiliation: Unité de Biologie et recherche Médicale, Centre National de l'Energie, des Sciences et Techniques Nucléaires (CNESTEN), Rabat, Morocco.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Attaleb
authors.forename: Wail
authors.initials: W
authors.lastname: El hamadani
authors.forename: Meriem
authors.initials: M
authors.lastname: Khyatti
authors.forename: Laila
authors.initials: L
authors.lastname: Benbacer
authors.forename: Nadia
authors.initials: N
authors.lastname: Benchekroun
authors.forename: Abdellatif
authors.initials: A
authors.lastname: Benider
authors.forename: Mariam
authors.initials: M
authors.lastname: Amrani
authors.forename: Mohammed
authors.initials: M
authors.lastname: El Mzibri
mesh_terms: D015820:Cadherins / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000821:virology; D018899:CpG Islands; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D027383:Papillomaviridae / Q000235:genetics; D030361:Papillomavirus Infections / Q000235:genetics / Q000473:pathology / Q000821:virology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology
chemical_list: D015820:Cadherins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D004279:DNA, Viral