Identification of Double-stranded Genomic DNA Spanning All Chromosomes with Mutated KRAS and p53 DNA in the Serum Exosomes of Patients with Pancreatic Cancer*

By Christoph Kahlert, S. Melo, A. Protopopov, Jiabin Tang, S. Seth, M. Koch, Jianhua Zhang, J. Weitz, L. Chin, A. Futreal and 1 more. Journal of Biological Chemistry, 2014

871 citations recorded by the source corpus.

Background: Exosomes are small vesicles in the tumor microenvironment containing nucleic acids and proteins with the capacity to influence cell behavior. Results: Exosomes contain double-stranded genomic DNA. Conclusion: Exosomes have the capacity to carry and transport genomic DNA spanning all chromosomes with KRAS and p53 mutations. Significance: Exosomes can aid in identifying genomic mutations in patients with pancreatic cancer. Exosomes are small vesicles (50–150 nm) of endocytic origin that are released by many different cell types. Exosomes in the tumor microenvironment may play a key role in facilitating cell-cell communication. Exosomes are reported to predominantly contain RNA and proteins. In this study, we investigated whether exosomes from pancreatic cancer cells and serum from patients with pancreatic ductal adenocarcinoma contain genomic DNA. Our results provide evidence that exosomes contain >10-kb fragments of double-stranded genomic DNA. Mutations in KRAS and p53 can be detected using genomic DNA from exosomes derived from pancreatic cancer cell lines and serum from patients with pancreatic cancer. In addition, using whole genome sequencing, we demonstrate that serum exosomes from patients with pancreatic cancer contain genomic DNA spanning all chromosomes. These results indicate that serum-derived exosomes can be used to determine genomic DNA mutations for cancer prediction, treatment, and therapy resistance.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/b0860cff68d04f11f510e1316077249dc997ea02

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Citations in the corpus

Extracellular vesicles in cancer: cell-to-cell mediators of metastasis (2016, background): “Importantly, exosomal dsDNA reflects the oncogenic mutational status of the respective parental cancer cell (Kahlert et al., 2014; Melo et al., 2015; Thakur et al., 2014), highlighting the utility of exosomal dsDNA as valuable biomarker for the detection of oncogenic mutations in the clinical…”
Innovative approaches for cancer treatment: current perspectives and new challenges (2019, methodology): “In recent years, exosomes detection has been validated as a reliable tool for preclinical practice in different cancer types [64], thanks to the identification of their content: double-stranded DNA (dsDNA) [65, 66], messenger RNA (mRNA), micro RNA (miRNA), long non-coding RNA (lncRNA) [67], proteins”
Characteristics and Significance of the Pre-metastatic Niche. (2016, background): “For instance, exosomes from the serum of pancreatic cancer patients carry and transport double-stranded genomic DNA with KRAS and p53 mutations (Kahlert et al., 2014).”
Inflammaging and 'Garb-aging'. (2017, background): “11 DNA but, notably, parts of it such as non-coding sequences, seem to be overrepresented, suggesting an active and selective vesicle compartmentalization of DNA molecules [60-62].”
Focus on Extracellular Vesicles: Introducing the Next Small Big Thing (2016, background): “Though the presence of mitochondrial DNA has not been validated by other groups, double stranded DNA (dsDNA) in tumor-derived EVs was also discovered and reported recently by several research groups [14–16].”
The biology and function of exosomes in cancer. (2016, background): “Additionally, driver mutations associated with pancreatic ductal adenocarcinoma (PDAC) were identified in this exosomal DNA (7).”
Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer (2017, neutral): “Furthermore, the composition of EV DNA and whether this molecule is inside the vesicles is still a conundrum (28).”