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 para...

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Autores principales:	Bella Nguyen, Nicholas C. Wong, Tim Semple, Michael Clark, Stephen Q. Wong, Connull Leslie, Bob Mirzai, Michael Millward, Katie Meehan, Annette M. Lim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a36570840ea1407d81af8c168aa6556e
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spelling	oai:doaj.org-article:a36570840ea1407d81af8c168aa6556e2021-12-02T14:03:45ZLow-coverage whole-genome sequencing of extracellular vesicle-associated DNA in patients with metastatic cancer10.1038/s41598-021-83436-12045-2322https://doaj.org/article/a36570840ea1407d81af8c168aa6556e2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83436-1https://doaj.org/toc/2045-2322Abstract 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.Bella NguyenNicholas C. WongTim SempleMichael ClarkStephen Q. WongConnull LeslieBob MirzaiMichael MillwardKatie MeehanAnnette M. LimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bella Nguyen Nicholas C. Wong Tim Semple Michael Clark Stephen Q. Wong Connull Leslie Bob Mirzai Michael Millward Katie Meehan Annette M. Lim Low-coverage whole-genome sequencing of extracellular vesicle-associated DNA in patients with metastatic cancer
description	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.
format	article
author	Bella Nguyen Nicholas C. Wong Tim Semple Michael Clark Stephen Q. Wong Connull Leslie Bob Mirzai Michael Millward Katie Meehan Annette M. Lim
author_facet	Bella Nguyen Nicholas C. Wong Tim Semple Michael Clark Stephen Q. Wong Connull Leslie Bob Mirzai Michael Millward Katie Meehan Annette M. Lim
author_sort	Bella Nguyen
title	Low-coverage whole-genome sequencing of extracellular vesicle-associated DNA in patients with metastatic cancer
title_short	Low-coverage whole-genome sequencing of extracellular vesicle-associated DNA in patients with metastatic cancer
title_full	Low-coverage whole-genome sequencing of extracellular vesicle-associated DNA in patients with metastatic cancer
title_fullStr	Low-coverage whole-genome sequencing of extracellular vesicle-associated DNA in patients with metastatic cancer
title_full_unstemmed	Low-coverage whole-genome sequencing of extracellular vesicle-associated DNA in patients with metastatic cancer
title_sort	low-coverage whole-genome sequencing of extracellular vesicle-associated dna in patients with metastatic cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a36570840ea1407d81af8c168aa6556e
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Low-coverage whole-genome sequencing of extracellular vesicle-associated DNA in patients with metastatic cancer

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