Low-coverage whole-genome sequencing of extracellular vesicle-associated DNA in patients with metastatic cancer.

Abstract

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.

• Authors: Bella Nguyen, Nicholas C Wong, Tim Semple, Michael Clark, Stephen Q Wong, Connull Leslie, Bob Mirzai, Michael Millward, Katie Meehan, Annette M Lim
• Journal: Scientific reports (Sci Rep) Vol. 11 Issue 1 Pg. 4016 (02 17 2021) ISSN: 2045-2322 [Electronic] England
• PMID: 33597619 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Formaldehyde

Topics

• Aged
• Biomarkers, Tumor (blood, genetics)
• Carcinoma, Squamous Cell (genetics, metabolism)
• DNA Copy Number Variations (genetics)
• Extracellular Vesicles (genetics, pathology)
• Female
• Formaldehyde (chemistry)
• Genome, Human (genetics)
• Genomics (methods)
• High-Throughput Nucleotide Sequencing (methods)
• Humans
• Male
• Middle Aged
• Mouth Neoplasms (genetics, metabolism)
• Neoplasm Metastasis (genetics, pathology)
• Neoplasms (genetics)
• Paraffin Embedding (methods)
• Tissue Fixation (methods)
• Whole Genome Sequencing (methods)