Exosomal DNA: Role in Reflecting Tumor Genetic Heterogeneity, Diagnosis, and Disease Monitoring
1
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan 430079, China
2
Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China
*
Authors to whom correspondence should be addressed.
Cancers 2024, 16(1), 57; https://doi.org/10.3390/cancers16010057
Submission received: 25 November 2023
/
Revised: 17 December 2023
/
Accepted: 19 December 2023
/
Published: 21 December 2023
(This article belongs to the Special Issue Exosomes in Tumor)
Simple Summary
Liquid biopsy is an emerging non-invasive biopsy technique. Compared to traditional tissue biopsy, it overcomes the challenges of tumor heterogeneity, allows for multiple sampling, dynamic real-time monitoring, and offers high sensitivity and specificity. Exploring stable and sensitive effective biopsy biomaterials is crucial. The objective of our research is to evaluate the biomarker role of DNA in exosomes, as exosomes demonstrate higher stability and detectability compared to currently used biopsy materials, but there is still a lack of research on exosomal DNA. We explored the formation and cargo loading mechanism of exosomes, summarized the research results on the relationship between mitochondrial DNA and nuclear DNA in exosomes with clinical tumors so far, and proposed several suggestions for the clinical application of exosomal DNA. Exosomal DNA has demonstrated valuable biomarker roles for certain tumors, providing guidance for clinical diagnosis, treatment, and disease monitoring.
Abstract
Extracellular vesicles (EVs), with exosomes at the forefront, are key in transferring cellular information and assorted biological materials, including nucleic acids. While exosomal RNA has been thoroughly examined, exploration into exosomal DNA (exoDNA)—which is stable and promising for cancer diagnostics—lags behind. This hybrid genetic material, combining contributions from both nuclear and mitochondrial DNA (mtDNA), is rooted in the cytoplasm. The enigmatic process concerning its cytoplasmic encapsulation continues to captivate researchers. Covering the entire genetic landscape, exoDNA encases significant oncogenic alterations in genes like TP53, ALK, and IDH1, which is vital for clinical assessment. This review delves into exosomal origins, the ins and outs of DNA encapsulation, and exoDNA’s link to tumor biology, underscoring its superiority to circulating tumor DNA in the biomarker arena for both detection and therapy. Amidst scientific progress, there are complexities in the comprehension and practical application of the exoDNA surface. Reflecting on these nuances, we chart the prospective research terrain and potential pitfalls, forging a path for future inquiry. By illuminating both the known and unknown facets of exoDNA, the objective of this review is to provide guidance to the field of liquid biopsy (LB) while minimizing the occurrence of avoidable blind spots and detours.
Keywords:
liquid biopsy; extracellular vesicles; exosomal DNA; biomarker
