Detection of epigenetic biomarkers in tissues and surveillance using saliva samples of bead and neck cancer patients

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Demokan S.


  • Publication Type: Article / Abstract
  • Volume: 40
  • Publication Date: 2017
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Istanbul University Affiliated: Yes


Recent studies have shown that epigenetic changes are effective in HNC. One of the most frequently observed and studied epigenetic mechanisms is DNA methylation. Methylation of CpG islands in the promoter regions of genes acts as a significant mechanism of epigenetic gene silencing. In our studies, we focused on identifying new methylation biomarkers or the methylation levels of known tumor suppressor genes in tissues and body fluids of the patients compared to healthy individuals. At present, we investigated the promoter methylation levels of EDNRB gene in post-treatment DNA obtained from the saliva of HNC patients as a prognostic marker for recurrent HNC by quantitative methylation-specific PCR. Fresh tumor samples and pre/post-treatment salivary rinses were collected from 76 patients with HNC. Post-treatment saliva samples were collected once in every 3 months. EDNRB gene was methylated in 96% and 73.6% of HNC tissues and pre-treatment salivary rinses from the same patients, respectively, whereas it was only methylated in 15.9% of the salivary rinses from normal subjects. EDNRB (85.7% specificity and 78.7% sensitivity) are highly sensitive marker that could potentially be used for molecular detection strategies. Patients with presence of methylation in surveillance salivary rinses are at significant risk for recurrence. New potential genes found as downregulated in tumor samples may play an important role in the development of premalignancy/malignancy as tumor suppressors and may be potential biological markers. For that purpose, in our new project supported by The Scientific and Technological Research Council of Turkey (TUBITAK-SBAG-114S497), we aimed to determine the molecular differences obtained by mRNA expression and methylation arrays in various subgroups of malignant / premalignant lesions of oral cavity on the basis of data obtained from healthy subjects. In the first part, methylation patterns of tumor and corresponding healthy tissues from Turkish patients with OPML and OSCC were investigated by using the Illumina Human Methylation 450 (Illumina, CA, USA) BeadChip array. According to our preliminary results obtained from the methylation array experiments, CpG regions in 6 genes were found unmethylated while CpGs located in one gene were highly methylated (p<0.005). Then, after getting the results from the expression array study, tumor and matched normal tissues were compared and found to be down-regulated at a significant level (p <0.05) of 42 and 35 genes respectively in OPML and OSCC patients. These potential candidate genes will be further validated in a larger group of patients‘ tissue and body fluids.