Mutational screening through comprehensive bioinformatics analysis to detect C۲۵۰T mutation in TERT promoter region among patients with brain tumor

Backgrounds: The principal mechanism of telomere maintenance, which plays a vital role inhuman tumorigenesis, is reactivation of telomerase reverse transcriptase. TERT promoter region(TERTp) mutations are common among solid tumors, particularly cancers originating from slowreplicatingtissues, like brain tumors. Furthermore, two most common mutations in this region(C۲۲۸T and C۲۵۰T) are considered as potential prognostic and diagnostic biomarkers of braintumors. Accordingly, detection of these mutations in cfDNA from a Liquid biopsy offers a lessinvasive tool in various steps of diagnosis and therapy.Materials and Methods: In this study, ۱۶ blood samples of brain tumor patients were collected.DNA extraction, polymerase chain reaction, gel electrophoresis and Sanger sequencing has beendone. Identified point mutation has been analyzed using two online tools, Softberry andPROMO, in order to predict its effect on TERTp reactivation.Results: C۲۵۰T mutation were recognized in ۸ samples including three glioblastoma multiforms,two pituitary gland tumors, one recurrent hemangioblastoma, one cerebellum tumor and anastrocytoma. Softberry indicated two de novo ETF binding sites. Similarly, PROMO showed twonew ETF binding sites in promoter region.Conclusion: This study indicated that C۲۵۰T as a hotspot mutation in TERTp region, leads to denovo ETF binding sites which can reactivate the gene. Additionally, C۲۵۰T where found in highgrad and recurrent samples. Due to the prevalence of this mutation among brain tumor tissues, itcan probably be considered as a biomarker for diagnosis and a landscape of tumor for patientfollow ups.

کلیدواژه ها:

Brain tumor ، Telomerase reactivation ، Telomerase reverse transcriptase ، TERTp ، cfDNA