Emergence of exosomal DNA in molecular neuropathology

Abstract

Background: Exosomes are small vesicles of sizes between 40 and 100 nm. They are actively segregated by numerous different cell types and they can be found in almost all body fluids. Thus, there is an emerging role of exosomes and exosomal deoxyribonucleic acid (exoDNA) in biomedical research, especially in molecular medicine. Exosomes are assembled and segregated actively and carry distinct surface markers for cellular communication. They are loaded with cargo such as DNA, ribonucleic acid (RNA) and proteins. As there are numerous different exosomal purification methods available, it is of essential need to select an appropriate technique to get reliable results. As neuropathology is faced with the challenge that brain tissue is not accessible in an easy fashion, exosomes represent an ideal tool for molecular neuro pathology. Thus, disease-specific molecular alterations will be detectable in a minimally invasive way for early disease diagnosis and surveillance. Summary: The analysis of exoDNA as biomarkers in neuropathology will enable early diagnosis, monitoring and relapse detection of brain tumors and neuropsychiatric disorders. Outlook: It is assumed that the significance of exosomes will increase in the upcoming years. There are powerful approaches in development using exosomes in molecularly targeted therapy to ultimately cure devastating brain diseases.

The Influence of a Stressful Microenvironment on Tumor Exosomes: A Focus on the DNA Cargo

“…It is important to note that the analysis of exosomal DNA has become particularly relevant when it is difficult to detect mutations prior to surgery, such as for neuronal tumors [ 52 , 53 ]. Serum exosomal dsDNA from patients with pheochromocytomas (PCCs) and paragangliomas (PGLs) shared the same mutations in ET, VHL, HIF2A, and SDHB genes with that of the parent tumor cells.…”

“…The detection of EGFR mutations in exosomes isolated from malignant pleural effusions [49,50] and KRAS and BRAF mutations in exosomes isolated from serum of patients with colorectal cancer [51] shows elevated sensitivity, specificity, and coincidence rate compared to tumor tissue analysis. The exosomal DNA isolated from ascites from patients with ovarian cancer reflects the copy number variation (CNV) status of the primary tumor [42] It is important to note that the analysis of exosomal DNA has become particularly relevant when it is difficult to detect mutations prior to surgery, such as for neuronal tumors [52,53]. Serum exosomal dsDNA from patients with pheochromocytomas (PCCs) and paragangliomas (PGLs) shared the same mutations in ET, VHL, HIF2A, and SDHB genes with that of the parent tumor cells.…”

Pro-Inflammatory Microenvironment Modulates the Transfer of Mutated TP53 Mediated by Tumor Exosomes

“…It has been shown that exosomal DNA can be used as a diagnostic marker in several pathologies [7], including tumor malignancies [8,9] and neurological disorders [10]. Tumor-derived microvesicles show higher DNA contents than those derived from normal cells [11,12].…”