Background: Ovarian cancer is the second most common gynecologic cancer with high mortality rate and generally diagnosed in advanced stages. The 5-year disease-free survival is below 40%. MicroRNAs, subset of the non-coding RNA molecules, regulate the translation in post transcriptional level by binding to specific mRNAs to promote or degrade the target oncogenes or tumor suppressor genes. Abnormal expression of miRNAs were found in numerous human cancer, including ovarian cancer. Investigating the miRNAs derived from the peripheral blood samples can be used as a marker in the diagnose, treatment and prognosis of ovarian cancer. We aimed to find biological markers for early diagnosis of ovarian cancer by investigating BRCA1 gene mutation carrier monozygotic discordant twins and their high risk healthy family individual’s miRNAs.Methods: The study was conducted on monozygotic twins discordant for ovarian cancer, and the liquid biopsy exploration of miRNAs was performed on mononuclear cells that were isolated from the peripheral blood samples. The miRNA expression profile changes in the study were found by using microarray analysis. miRNA isolation procedure performed from the lymphocyte in accordance with the kit protocol. The presence and quality of the isolated miRNAs screened by electrophoresis. Raw data logarithmic analysis was studied by identifying the threshold, normalization, correlation, mean and median values. Target proteins were detected for each miRNA by using different algorithms.Results: After the comparison of monozygotic discordant twins for epithelial ovarian carcinoma upregulation of the 4 miRNAs, miR-6131, miR-1305, miR-197-3p, miR-3651 and downregulation of 4 miRNAs, miR-3135b, miR-4430, miR-664b-5p, miR-766-3p were found statically significant.Conclusions: The detected 99 miRNAs out of 2549 miRNAs might be used in the clinic as new biological indicators in the diagnosis and follow up of epithelial ovarian cancer with complementary studies. ThemiRNA expressionprofiles were identified to be statistically significant in the evaluation of ovarian cancer etiology, BRCA1 mutation status, and ovarian cancer risk in accordance with the obtained data.There is a need for validation of the miRNAs which were particularly detected between monozygotic twins and its association with ovarian cancer was emphasized in our study in wider cohorts including ovarian cancer patients, and healthy individuals.

Ovarian cancer is a disease that is generally diagnosed at an advanced stage, and has poor survival. Monozygotic (MZ) twins are considered to be good research models for investigating the epigenetic changes associated with diseases. In the present study, the involvement of epigenetic mechanisms in ovarian cancer etiology were evaluated using the MZ twin model. Whole‑genome methylation patterns were investigated in a BRCA1 gene mutation‑carrying family comprising MZ twins, only one of whom had ovarian cancer, and other healthy siblings. Whole‑genome methylation patterns were assessed in peripheral blood DNA using Infinium MethylationEPIC BeadChips on an Illumina iScan device. The hypermethylated and hypomethylated genes were detected between cases and controls in four different comparison groups in order to evaluate the differences in methylation levels according to cancer diagnosis and BRCA mutation status. The obtained results showed that the differential methylations in 12 different genes, namely PR/SET domain 6, cytochrome B5 reductase 4, ZNF714, OR52M1, SEMA4D, CHD1L, CAPZB, clustered mitochondria homolog, RB‑binding protein 7, chromatin repair factor, ankyrin repeat domain 23, RIB43A domain with coiled‑coils 1 and C6orf227, were associated with ovarian cancer. Biological functional analysis of the genes detected in the study using the PANTHER classification system revealed that they have roles in biological processes including ‘biologic adhesion’, ‘regulation’, ‘cellular components organization’, ‘biogenesis’, ‘immune system functioning’, ‘metabolic functioning’ and ‘localization’. Overall, the present study suggested that epigenetic differences, such as methylation status, could be used as a non‑invasive biological markers for the early diagnosis and follow‑up of ovarian cancer.

Eur J Breast Health AVES | Copyright © 2017 Türkiye Meme Hastalıkları Dernekleri Federasyonu |

Objectives: To find BRCA1/2 test selection criteria unique to the Turkish population, as well as to provide the BRCA1/2 gene mutation distributions of patient population to the literature. Methods: Genetic counseling was given to 2,373 cases with a family history of high-risk breast and/or ovarian cancer who applied to Istanbul University, Oncology Institute, Department of Cancer Genetics between 1994 and 2021 and selected by NCCN Guidelines for the BRCA1/2 test criteria. In our clinic, mutation screenings in BRCA1/2 genes were performed by Sanger sequencing method in patients admitted between 1994 and 2014 and by NGS method in patients admitted between 2015 and 2021. Results: The overall mutation rate in our patient group selected from high-risk patients was 16.5% (391/2,373) after BRCA1/2 gene mutation screening performed in 2,373 cases who applied to the Cancer Genetics clinic. Of the patients with mutations, 57.5% (225/391) had BRCA1 mutation, 41.9% (164/391) had BRCA2 mutation, and 0.6% (2/391) had both BRCA1 and BRCA2 pathogenic mutations. People diagnosed before the age of 60 who have a history of triple-negative breast cancer had a 28.5% overall mutation rate. Conclusions: BRCA1/2 mutation in Turkish population were evaluated in accordance with NCCN BRCA1/2 genetic test selection criteria; we discovered that all of our study results were statistically significant (p<0.05).

Aim The prevalence of BRCA1/2 pathogenic variants among Turkish breast cancer (BC) patients is not well-characterized. We specifically examine the age at onset and cancer sub-types concerning BRCA1/2 mutation status, focusing on patients with no family history of breast or ovarian cancer. Methods Peripheral blood samples were collected from 3184 BC patients applied to the Istanbul University Oncology Institute. Genetic testing for BRCA1/2 mutations was conducted using the Illumina MiSeq® platform, with variant classification performed according to ACMG criteria. Results Among the 3184 patients, 2764 (86.8%) were BRCA1/2-, while 247 (7.8%) were BRCA1 + and 173 (5.4%) were BRCA2 + . The mean age at BC onset was significantly lower in BRCA1 + (39.73 years) and BRCA2 + (41.07 years) patients compared to BRCA1/2- patients (43.17 years, p < 0.001). Among patients with no family history, HER2 positive cases had a significantly higher mean age at onset than Triple-Negative Breast Cancer(TNBC) cases (41.78 years vs. 40.44 years, p = 0.017). Conclusions This study highlights the strong association between BRCA1/2 + mutations and earlier BC onset, particularly in patients with no family history of breast or ovarian cancer in Türkiye.