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.

Background Triple-negative breast cancer (TNBC) lacks expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Genetic mutations, particularly in BRCA1 and BRCA2, significantly influence its pathogenesis and clinical outcomes. This study evaluated the prevalence of BRCA1 and BRCA2 mutations in Turkish TNBC patients and investigated associated clinical, demographic, and pathological factors. Materials and methods Patients with TNBC who presented to the Cancer Genetics Department at Istanbul University Oncology Institute were included. Peripheral blood mononuclear cells were analyzed for BRCA1 and BRCA2 mutations using the Illumina MiSeq Next Generation Sequencing (NGS) platform. Patients were categorized as BRCA1 + or BRCA2+ (mutation carriers) or BRCA1- or BRCA2- (mutation non-carriers). Comparative analyses were conducted to identify differences between groups, and clustering analysis examined mutation patterns. Results Among 485 TNBC patients, 119 (24.5%) carried pathogenic variants in BRCA1 and/or BRCA2 genes. Of these 119 carriers, 4 (0.8% of the total) harbored mutations in both genes. Specifically, 101 (20.8%) had BRCA1 + mutations, and 22 (4.5%) had BRCA2 + mutations. The carrier group had higher rates of bilateral breast cancer (BC) (14.3% vs. 4.9%), a family history of breast and ovarian cancer (BC and OC) (51.3% vs. 26%), and increased first-degree relative cancer cases. Bilateral BC was associated with a 2.748-fold increased risk of BRCA1 + mutations, while postmenopausal status reduced risk by 0.350-fold. Each additional first-degree BC case increased BRCA1 + mutation risk by 2.410-fold. Cluster analysis identified two distinct mutation patterns. Conclusion Turkish TNBC patients with BRCA1 + or BRCA2 + mutations exhibit unique clinical and familial characteristics, emphasizing the importance of genetic screening and familial risk evaluation in TNBC management. These findings underscore the clinical relevance of BRCA testing in TNBC patients for personalized screening and treatment strategies. Notably, this study provides the largest TNBC cohort (n = 485) reported from Türkiye, highlighting the significant role of BRCA1 in TNBC pathogenesis and offering a roadmap for individualized management.

The process of RNA splicing is fundamental in contributing to proteomic diversity and regulating gene expression. Dysregulation of splicing is associated with various human disorders, including cancer. Through functional studies, this study sought to examine the potential impact of seven variants within six inherited cancer-related genes on RNA splicing patterns in Turkish cancer patients. Upon detecting variants using Next-Generation Sequencing (NGS), we used Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) and Sanger sequencing to elucidate the effects of these variants on splicing. Three of the seven variants demonstrated no discernible effect on RNA, while four exhibited pathogenic characteristics. Specifically, the variants APC c.532-1G>A rs1554072547, BRCA1c.4358-3A>G rs1567779966, BRCA2c.7436-1G>C rs81002830 and MSH3c.1897-1G>A rs1744149615 were identified as pathogenic, while the variants BLMc.4076+4T>G rs183176301, RB1c.2489+2T>C rs1555294636 and RB1c.1050-2A>G rs? were found to be benign from a splicing perspective. These findings highlight the importance of verifying the precise consequences of splice-site variants through experimental analysis, given their potential implications for genetic disorders and cancer predisposition. This research contributes to the understanding of splice-site variants in inherited cancer predisposition, particularly among Turkish cancer patients. It emphasizes the necessity for further exploration into the mechanisms and functional consequences of alternative splicing for potential therapeutic interventions in cancer.

Objectives: Colon cancer (CC) remains one of the leading causes of cancer-related mortality worldwide, and reliable non-invasive biomarkers for disease staging and monitoring are still lacking. Exosomal microRNAs (miRNAs) have emerged as promising candidates for liquid biopsies due to their stability and tumor-specific expression profiles. This pilot study evaluated the diagnostic potential of four serum exosomal miRNAs, miR-30b-3p, miR-99a-5p, miR-769-5p, and miR-3937, in differentiating CC patients (n=28) from healthy controls (n=20), and primary (n=24) from metastatic tumors (n=4). Methods: Exosomal RNA was isolated and quantified using digital polymerase chain reaction (dPCR). Results: miR-30b-3p and miR-3937 were upregulated in patients vs. controls, while miR-30b-3p showed a striking 67.8-fold higher expression in primary compared with metastatic tumors (AUC=0.771). Conversely, miR-99a-5p was elevated 5.4-fold in metastatic tumors. Combined miRNA panels improved performance, with the miR-30b-3p/miR-99a-5p/miR-3937 panel achieving an AUC of 0.932, suggesting synergistic diagnostic value. Conclusions: This study provides preliminary evidence supporting exosomal miR-30b-3p as a potential liquid biopsy biomarker for stage-specific detection of CC, warranting validation in larger cohorts.

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by impaired differentiation and accumulation of immature myeloid cells. Aurora kinases and their regulatory genes play key roles in mitotic progression and may contribute to leukemogenesis. This study aimed to evaluate the expression and promoter methylation status of AURKA, AURKB, and AURKC and their regulatory genes, AURKAIP1, E2F1, and E2F4 in AML. Peripheral blood samples from 83 AML patients and 28 age- and sex-matched healthy controls were analyzed using MIQE-compliant RT-qPCR for gene expression and MSRE-qPCR for promoter methylation. Diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis. Expression levels of AURKA, AURKB, AURKC, and E2F1 were significantly increased in AML patients (p < 0.001), whereas AURKAIP1 expression was significantly reduced (p = 0.001), and E2F4 showed no significant difference. Promoter methylation analysis revealed significantly increased AURKAIP1 methylation in AML (p < 0.001), decreased E2F4 methylation (p = 0.023), and no significant change in E2F1. ROC analysis demonstrated strong diagnostic performance, with AURKB showing the highest accuracy (AUC = 0.95), while a combined biomarker panel achieved an AUC of 0.96. Aurora kinase–related genes are dysregulated in AML and may serve as preliminary peripheral biomarker candidates. However, further validation in independent cohorts and more refined cellular models is required before clinical application.