The role of next-generation sequencing in the examination of signaling genes in Brca1/2-negative breast cancer cases.

INTRODUCTION: Breast cancer is the most prevalent malignancy in women worldwide. Although pathogenic variants in the BRCA1/2 genes are responsible for the majority of hereditary breast cancer cases, a substantial proportion of patients are negative for pathogenic variations in these genes. In cancers, the signal transduction pathways of the cell are usually affected first. Therefore, this study aimed to detect and classified genetic variations in non-BRCA signaling genes and investigate the underlying genetic causes of susceptibility to breast cancer. METHODS: Ninety-six patients without pathogenic variants in the BRCA1/2 genes who met the inclusion criteria were enrolled in the study, and 34 genes were analyzed using next-generation sequencing (NGS) for genetic analysis. RESULTS: Based on the ClinVar database or American College of Medical Genetics criteria, a total of 55 variants of 16 genes were detected in 43 (44.8%) of the 96 patients included in the study. The pathogenic variants were found in the TP53, CHEK2, and RET genes, whereas the likely pathogenic variants were found in the FGFR1, FGFR3, EGFR, and NOTCH1 genes. CONCLUSION: The examination of signaling genes in patients who met the established criteria for hereditary breast cancer but were negative for BRCA1/2 pathogenic variants provided additional information for approximately 8% of the families. The results of the present study suggest that NGS is a powerful tool for investigating the underlying genetic causes of occurrence and progression of breast cancer.

The diagnostic importance of pathogenic variants and variant coexistence determined by NGS-based liquid biopsy approach in patients with lung adenocarcinoma.

BACKROUND: Identification of driver mutations and rapid detection of genetic changes in lung cancer are critical in the management of the disease. Genetic structures of tumor tissues tend to change constantly and the possibility of emergence of new pathogenic variants that will create resistance to treatment. Liquid biopsy analysis has been one of the most effective approaches used to monitor and identify individual genetic changes. METHODS: In this study, TP53, EGFR, MET, ALK, PIK3CA, MAP2K, ERBB2 and ROS genes in cf DNA samples of 324 patients with lung adenocarcinoma were screened for genetic variations by NGS method. Analysis of the data showed that there were a total of 755 variations in 324 patients. RESULTS: Pathogenic and possibly pathogenic variations were identified in 178 patients (54.9%) on TP53, 118 (36.4%) on EGFR, 55 (17.0%) on MET, 46 (14.2%) on ALK, 39 (12.0%) on MAP2K, 6 (1.9%) on ERBB2 and in 2 (0,6%) patients ROS genes. The detailed variant data of the genes included in the study were compared with the patients' stage status, metastasis status, smoking, age distribution and life span data, and the presence of possible significant relationships and candidate biomarkers for the molecular pathogenesis of the disease were investigated. CONCLUSION: As a result of data analysis, genetic changes associated with metastasis and adenocarcinoma formation were identified. It has been shown that variations identified in TP53, PIK3CA, MAP2K1 and EGFR genes can play critical roles in the pathogenesis and development of the disease.

TP53, EGFR and PIK3CA gene variations observed as prominent biomarkers in breast and lung cancer by plasma cell-free DNA genomic testing.

Use of plasma cell-free DNA genomic testing, also know as liquid biopsy, reveals information for early detection and monitoring of solid tumors. Our study reports the analysis of 113 lung and 18 breast cancer patients using commercially available platforms. Lung and breast cancer panel hotspot regions on the genes were investigated. There was a significant increase in isolation efficiency with very fresh blood samples of at least 15 millilitres which were processed in minutes. TP53 gene variations were detected in both types of tumors. Additionally, associations were found for EGFR variations in lung tumors and PIK3CA variations in breast tumors. Mutation assessment of these three genes are recommended as useful biomarkers for predictive studies, to follow up tumor growth and for personalized treatment. Mutations observed in this study warrant further investigation for follow up studies and may justify expression studies. However, in our subsequent studies, we intensify our tumor profiling strategy with other methods. However in terms of true personalized medicine,future plans would include repeating these studies with ctDNA size analysis and methylation analysis of the non-coding region in the individual tumors.

A CGH array study in nonsyndromic (primary) autism patients: deletions on 16p13.11, 16p11.2, 1q21.1, 2q21.1q21.2, and 8p23.1.

BACKGROUND/AIM: To detect specific molecular changes of DNA level in primary autism patients by using whole genome CGH array technology. MATERIALS AND METHODS: A cohort of 35 primary autism patients received clinical genetic testing by using an oligonucleotide-based CGH array platform to test for submicroscopic genomic deletions and duplications. Fluorescent in situ hybridization was performed in seven patients for confirmation of the results. RESULTS: We found 16p13.11 deletion in thirteen patients, 16p11.2 deletion in twelve patients, 1q21.1 deletion in ten patients, 2q21.1q21.2 deletion in eight patients, and 8p23.1 deletion in seven patients. CONCLUSION: Our study indicates that genes in 16p13.11, 16p11.2, 1q21.1, 2q2l.1q21.2, and 8p23.1 loci are potential predisposition and new suspicious regions for primary autism. Deletion's in these regions should be investigated in further studies to understand pathogenesis of primary autism.