期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2022.1028854
关键词
tumor-derived extracellular vesicles; melanoma; DNA; ultrasensitive DNA sequencing; SiMSen-Seq
资金
- Cancer Foundation [2017/739]
- VR [2016-02854]
- Knut and Alice Wallenberg Foundation
- Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Sweden
- Assar Gabrielssons Foundation
- Johan Jansson Foundation for Cancer Research
- Region Vaestra Goetaland
- Swedish Cancer Society [19-0306]
- Swedish Research Council [2020-01008]
- Swedish government
- county councils
- ALF [965065]
- Sweden's Innovation Agency [2018-00421, 2020-04141]
- Sjoeberg Foundation
- Formas [2018-00421] Funding Source: Formas
- Swedish Research Council [2016-02854] Funding Source: Swedish Research Council
- Vinnova [2018-00421, 2020-01008] Funding Source: Vinnova
This study identified tumor-specific DNA mutations in EVs isolated from melanoma metastatic tissues, showing a higher mutant allele frequency in DNA isolated from tumor-derived EVs compared to total plasma DNA, indicating the potential role of tumor EVs as future biomarkers in melanoma.
Liquid biopsies are promising tools for early diagnosis and residual disease monitoring in patients with cancer, and circulating tumor DNA isolated from plasma has been extensively studied as it has been shown to contain tumor-specific mutations. Extracellular vesicles (EVs) present in tumor tissues carry tumor-derived molecules such as proteins and nucleic acids, and thus EVs can potentially represent a source of cancer-specific DNA. Here we identified the presence of tumor-specific DNA mutations in EVs isolated from six human melanoma metastatic tissues and compared the results with tumor tissue DNA and plasma DNA. Tumor tissue EVs were isolated using enzymatic treatment followed by ultracentrifugation and iodixanol density cushion isolation. A panel of 34 melanoma-related genes was investigated using ultra-sensitive sequencing (SiMSen-seq). We detected mutations in six genes in the EVs (BRAF, NRAS, CDKN2A, STK19, PPP6C, and RAC), and at least one mutation was detected in all melanoma EV samples. Interestingly, the mutant allele frequency was higher in DNA isolated from tumor-derived EVs compared to total DNA extracted directly from plasma DNA, supporting the potential role of tumor EVs as future biomarkers in melanoma.
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