Assessment of epigenetic alterations and in silico analysis of mutation affecting PTEN expression among Indian cervical cancer patients. Issue 9 (9th May 2019)

• Record Type: Journal Article
• Authors: Naseem, Afreen; Bhat, Zafar Iqbal; Kalaiarasan, Ponnusamy; Kumar, Bhupender; Bin Hafeez, Zubair; Tiwari, Raj Ranjan; Wahabi, Khushnuma; Gandhi, Gauri; Alam Rizvi, M. Moshahid
• Is Part Of: Journal of cellular biochemistry. Volume 120:Issue 9(2019)
• Page Start: 15851
• Page End: 15866
• Publication Date: 2019-05-09
• Subjects: cervical cancer -- epidermal growth factor receptor -- molecular dynamics simulations -- promoter hypermethylation -- phosphatase and tensin homolog; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.28856
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: Genetic and epigenetic anomalies accountable for genetic dysregulation are the most common aberrations that determine the underlying heterogeneity of the tumor cells. Currently, phosphatase and tensin homolog (PTEN) incongruity has emerged as potent and persuasive malfunctioning in varied human malignancies. In this study, we have analysed the promoter hypermethylation and expression status of PTEN. We identified different mutations in the exonic region of PTEN . Functional consequences of these mutations were explored using in silico techniques. Promoter hypermethylation of PTEN was detected using methylation‐specific polymerase chain reaction (MS‐PCR), expression analysis was performed with immunohistochemistry (IHC) and mutation by direct sequencing in a total of 168 uterine cervix tumor cases. The findings were statistically correlated with the clinical parameters. In addition, the effect of nonsynonymous mutations was studied with molecular dynamics simulations. PTEN promoter hypermethylation (45.8%) was found to be significantly associated with the of PTEN loss (57.14%, P < 0.0001). Tumor stages, tumor size, lymph node (LN) were found to be significantly correlated with both PTEN promoter hypermethylation and PTEN loss. Histological grade, however, showed a significant association with only PTEN loss. In total, 11.76% of tumors exhibited mutations in exon 5 and 7, out of which E150K of exon 5 showed the highest deviations in the crystal structure of PTEN by in silico analysis. This study provides valuable insights into oncology and paves the path in the development of efficient biomarker and/or imperative therapeutic tool for cervical cancer treatment. Abstract : Epigenetic alterations and in silico analysis of mutation disturbing phosphatase and tensin homolog (PTEN) expression among cervical cancer patients.