Türk popülasyonunda over kanseri hastalarinda TERT geninin yeni nesil dizileme yöntemiyle mutasyon analizi

Ovarian cancer is the most common gynecological cancer after uterine cancer in our country. Although the frequency of the disease varies among different racial and ethnic groups, it is higher in developed countries than in developing countries. It affects women of all ages. Epithelial tumors constitute the majority of malignant ovarian tumors. Various risk factors are known to be associated with an increased risk of ovarian cancer. Among these risk factors, especially genetic factors, are responsible for the increased risk of developing ovarian cancer. Mutations are inherited changes in genetic material and are important because they can cause cancer. Most of the mutations in TERT, ATRX, MGMT, and IDH genes are associated with the risk of multiple cancer types. The Next Generation Sequencing approach is used in cancer studies, including ovarian cancer, facilitating the identification of existing mutations as well as new discoveries. In our study, 33 female patients between the ages of 18 and 76 who were diagnosed with ovarian cancer at Yeditepe University hospital and had demographically identical characteristics were included. With their consent, DNA was isolated from the blood samples collected from the patients, and significant and nonsense mutations in the IDH1, IDH2, TERT, MGMT, and ATRX genes were detected using the Next Generation Sequencing method. A bioinformatics analysis study was carried out with the Illumina Data Analysis Program. 7 different variants of the TERT gene were observed in 24 to 33 patients. Mutations were seen in both exonic and intronic regions. In our study, in the TERT gene, heterozygous in 7 patients and homozygous in 1 patient, c.2850-3039C>T; (p.H950H, p.H1013H) mutation, heterozygous in 2 patients c.2517G>A;(p.T839T) mutation, heterozygous in 1 patient, c.2031C>T; (p.G677G) mutation, heterozygous in 3 patients c.835G>A (p.A279T) mutation, heterozygous in 1 patient c.1392C>T; (p.F464F) mutation, heterozygous in 1 patient c.2995-3184G>A; (p.A1062T, p.A999T) mutation and heterozygous in 16 patients and homozygous in 3 patients c.915G>A; (p.A305A) mutations have been detected. Among the 7 different variants seen in the study, variants of unknown clinical significance were detected. For the other genes included in our study, 5 variants in the ATRX gene, 3 variants in the IDH1 gene, 1 variant in the IDH2 gene, and 6 variants in the MGMT gene were detected. A c.699-3delC deletion was observed in one patient in the intronic region of the IDH1 gene, and the c.532G > A (p.V178I) mutation seen in 3 patients was evaluated as possibly harmful. In addition, novel variant c.881A > G ; c.995A > G was detected in the ATRX gene. The heterozygous novel variant detected in the ATRX gene was confirmed to be heterozygous by Sanger sequencing.The variants of TERT, IDH1, IDH2, MGMT, and ATRX genes we found in our study were evaluated by comparing them with existing databases and literature. The variants we found were not previously associated with ovarian cancer and were evaluated as a new marker candidate for ovarian cancer susceptibility. If our results are confirmed by future studies with larger cohorts or functional studies, our findings will contribute significantly to elucidating the molecular mechanisms of ovarian cancer. Key Words: Over cancer, Tert, polymorphisms