Circulating exosomal miRNAs as a promising diagnostic biomarker in cancer.

Cancer belongs to multifactorial diseases characterized by uncontrolled growth and proliferation of abnormal cells. Breast cancer, non-small cell lung cancer, and colorectal cancer are the most frequently diagnosed malignancies with a high mortality rate. These carcinomas typically contain multiple genetically distinct subpopulations of tumor cells leading to tumor heterogeneity, which promotes the aggressiveness of the disease. Early diagnosis is necessary to increase patient progression-free survival. Particularly, miRNAs present in exosomes derived from tumors represent potential biomarkers suitable for early cancer diagnosis. Identification of miRNAs by liquid biopsy enables a personalized approach with the subsequent better clinical management of patients. This review article highlights the potential of circulating exosomal miRNAs in early breast, non-small cell lung, and colorectal cancer diagnosis.

Comprehensive Genomic Profiling in Predictive Testing of Cancer.

Despite the rapid progress in the field of personalized medicine and the efforts to apply specific treatment strategies to patients based on the presence of pathogenic variants in one, two, or three genes, patient response to the treatment in terms of positive benefit and overall survival remains heterogeneous. However, advances in sequencing and bioinformatics technologies have facilitated the simultaneous examination of somatic variants in tens to thousands of genes in tumor tissue, enabling the determination of personalized management based on the patient's comprehensive genomic profile (CGP). CGP has the potential to enhance clinical decision-making and personalize innovative treatments for individual patients, by providing oncologists with a more comprehensive molecular characterization of tumors. This study aimed to highlight the utility of CGP in routine clinical practice. Here we present three patient cases with various advanced cancer indicated for CGP analysis using a combination of SOPHiA Solid Tumor Solution (STS, 42 genes) for DNA and SOPHiA RNAtarget Oncology Solution (ROS, 45 genes and 17 gene fusions with any random partners) for RNA. We were able to identify actionable genomic alterations in all three cases, thereby presenting valuable information for future management of these patients. This approach has the potential to transform clinical practice and greatly improve patient outcomes in the field of oncology.

Rapid screening test of most frequent BRCA1/BRCA2 pathogenic variants in the NGS era.

The average risk of breast cancer in general Slovak population of women is 4-5% and the risk of ovarian cancer is 2%. Probability of breast/ovarian cancer development is higher in individuals carrying a causative germline DNA variant in BRCA1 or BRCA2 gene responsible for hereditary breast/ovarian cancer (HBOC). Although a major proportion of inherited breast/ovarian cancers are due to the mentioned causal mutations, a number of new genes have emerged. Here we describe a rapid, multiplex and comprehensive approach for the detection of pathogenic variants in BRCA1 and BRCA2 genes which most frequently occur in Slovak HBOC population. Analysis comprises the combination of mutation specific methods. Fluorescent PCR amplification followed by fragment analysis for detection of insertions/deletions in exon 11 of BRCA1 gene. Second method is SNaPshot analysis for detection of the most frequent missense and ins/del variants in exons 2, 5, 13, 20 of BRCA1 and exons 11, 23 and 25 of BRCA2 gene. Altogether, we have analyzed 687 samples, 86 (12.5%) in group 1, which fulfilled indication criteria based on the positive family/personal history. Group 2 involved 601 (87.5%) cases, who did not meet the indication criteria and only the screening test was recommended. Using the combined approach, we have identified 47 mutated samples (6.8%), 40 in group 1 (46.5%) and 7 in group 2 (1.1%). However, the presented screening test would not provide complex results of BRCA1/2 gene analysis, it offers testing accessible to a broader spectrum of individuals under the threshold of indication for whole gene analysis. This approach may provide valuable information even in the NGS analysis era.