Document Type
Journal Article
Publication Title
Scientific Reports
Volume
11
Issue
1
PubMed ID
33597619
Publisher
Nature
School
School of Medical and Health Sciences
RAS ID
39581
Funders
Funding information : https://www.nature.com/articles/s41598-021-83436-1
Abstract
© 2021, The Author(s). Low-coverage whole-genome sequencing (LC-WGS) can provide insight into oncogenic molecular changes. Serum extracellular vesicles (EV) represent a novel liquid biopsy source of tumoral DNA. This study compared copy number alteration (CNA) profiles generated from LC-WGS of formalin-fixed paraffin-embedded (FFPE) tumoral DNA and EV-DNA obtained from cancer patients. Patients with squamous cell carcinoma of the base of tongue (n = 3) and cutaneous squamous cell carcinoma (n = 2) were included. LC-WGS (0.5-1X coverage) was performed on FFPE-DNA and serum EV-DNA. Similarity between CNA profiles was analysed using QDNAseq. FFPE samples had a mean CNA of 31 (range 17–50) over 1.9 × 109 (range 1.0–2.6 × 109) bp in length, and EV samples had a mean CNA value of 17 (range 7–19) over 7.6 × 108 (range 2.9–15 × 108) bp in length. A mean of 8 (range 0–21) CNA over 5.9 × 108 (range 1.6–14 × 108) bp in length was found to overlap between EV and FFPE-derived samples per patient. Although the mean correlation efficient between samples was r = 0.34 (range − .08 to 0.99), this was not statistically significant (p > 0.05). Regions of highest deletion and duplication in FFPE samples were not well reflected in the EV-DNA. Selected CNA regions in EV-associated DNA were reflective of the primary tumor, however appreciation of global CNA and areas of most significant change was lost. The utility of LC-WGS of EV-derived DNA is likely limited to molecular alterations of known interest.
DOI
10.1038/s41598-021-83436-1
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Nguyen, B., Wong, N. C., Semple, T., Clark, M., Wong, S. Q., Leslie, C., ... Lim, A. M. (2021). Low-coverage whole-genome sequencing of extracellular vesicle-associated DNA in patients with metastatic cancer. Scientific Reports, 11, article 4016. https://doi.org/10.1038/s41598-021-83436-1