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Cell-free tumour DNA analysis detects copy number alterations in gastro-oesophageal cancer patients
BACKGROUND: Analysis of cell-free tumour DNA, a liquid biopsy, is a promising biomarker for cancer. We have performed a proof-of principle study to test the applicability in the clinical setting, analysing copy number alterations (CNAs) in plasma and tumour tissue from 44 patients with gastro-oesoph...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861431/ https://www.ncbi.nlm.nih.gov/pubmed/33539436 http://dx.doi.org/10.1371/journal.pone.0245488 |
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author | Wallander, Karin Eisfeldt, Jesper Lindblad, Mats Nilsson, Daniel Billiau, Kenny Foroughi, Hassan Nordenskjöld, Magnus Liedén, Agne Tham, Emma |
author_facet | Wallander, Karin Eisfeldt, Jesper Lindblad, Mats Nilsson, Daniel Billiau, Kenny Foroughi, Hassan Nordenskjöld, Magnus Liedén, Agne Tham, Emma |
author_sort | Wallander, Karin |
collection | PubMed |
description | BACKGROUND: Analysis of cell-free tumour DNA, a liquid biopsy, is a promising biomarker for cancer. We have performed a proof-of principle study to test the applicability in the clinical setting, analysing copy number alterations (CNAs) in plasma and tumour tissue from 44 patients with gastro-oesophageal cancer. METHODS: DNA was isolated from blood plasma and a tissue sample from each patient. Array-CGH was applied to the tissue DNA. The cell-free plasma DNA was sequenced by low-coverage whole-genome sequencing using a clinical pipeline for non-invasive prenatal testing. WISECONDOR and ichorCNA, two bioinformatic tools, were used to process the output data and were compared to each other. RESULTS: Cancer-associated CNAs could be seen in 59% (26/44) of the tissue biopsies. In the plasma samples, a targeted approach analysing 61 regions of special interest in gastro-oesophageal cancer detected cancer-associated CNAs with a z-score >5 in 11 patients. Broadening the analysis to a whole-genome view, 17/44 patients (39%) had cancer-associated CNAs using WISECONDOR and 13 (30%) using ichorCNA. Of the 26 patients with tissue-verified cancer-associated CNAs, 14 (54%) had corresponding CNAs in plasma. Potentially clinically actionable amplifications overlapping the genes VEGFA, EGFR and FGFR2 were detected in the plasma from three patients. CONCLUSIONS: We conclude that low-coverage whole-genome sequencing without prior knowledge of the tumour alterations could become a useful tool for cell-free tumour DNA analysis of total CNAs in plasma from patients with gastro-oesophageal cancer. |
format | Online Article Text |
id | pubmed-7861431 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-78614312021-02-12 Cell-free tumour DNA analysis detects copy number alterations in gastro-oesophageal cancer patients Wallander, Karin Eisfeldt, Jesper Lindblad, Mats Nilsson, Daniel Billiau, Kenny Foroughi, Hassan Nordenskjöld, Magnus Liedén, Agne Tham, Emma PLoS One Research Article BACKGROUND: Analysis of cell-free tumour DNA, a liquid biopsy, is a promising biomarker for cancer. We have performed a proof-of principle study to test the applicability in the clinical setting, analysing copy number alterations (CNAs) in plasma and tumour tissue from 44 patients with gastro-oesophageal cancer. METHODS: DNA was isolated from blood plasma and a tissue sample from each patient. Array-CGH was applied to the tissue DNA. The cell-free plasma DNA was sequenced by low-coverage whole-genome sequencing using a clinical pipeline for non-invasive prenatal testing. WISECONDOR and ichorCNA, two bioinformatic tools, were used to process the output data and were compared to each other. RESULTS: Cancer-associated CNAs could be seen in 59% (26/44) of the tissue biopsies. In the plasma samples, a targeted approach analysing 61 regions of special interest in gastro-oesophageal cancer detected cancer-associated CNAs with a z-score >5 in 11 patients. Broadening the analysis to a whole-genome view, 17/44 patients (39%) had cancer-associated CNAs using WISECONDOR and 13 (30%) using ichorCNA. Of the 26 patients with tissue-verified cancer-associated CNAs, 14 (54%) had corresponding CNAs in plasma. Potentially clinically actionable amplifications overlapping the genes VEGFA, EGFR and FGFR2 were detected in the plasma from three patients. CONCLUSIONS: We conclude that low-coverage whole-genome sequencing without prior knowledge of the tumour alterations could become a useful tool for cell-free tumour DNA analysis of total CNAs in plasma from patients with gastro-oesophageal cancer. Public Library of Science 2021-02-04 /pmc/articles/PMC7861431/ /pubmed/33539436 http://dx.doi.org/10.1371/journal.pone.0245488 Text en © 2021 Wallander et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Wallander, Karin Eisfeldt, Jesper Lindblad, Mats Nilsson, Daniel Billiau, Kenny Foroughi, Hassan Nordenskjöld, Magnus Liedén, Agne Tham, Emma Cell-free tumour DNA analysis detects copy number alterations in gastro-oesophageal cancer patients |
title | Cell-free tumour DNA analysis detects copy number alterations in gastro-oesophageal cancer patients |
title_full | Cell-free tumour DNA analysis detects copy number alterations in gastro-oesophageal cancer patients |
title_fullStr | Cell-free tumour DNA analysis detects copy number alterations in gastro-oesophageal cancer patients |
title_full_unstemmed | Cell-free tumour DNA analysis detects copy number alterations in gastro-oesophageal cancer patients |
title_short | Cell-free tumour DNA analysis detects copy number alterations in gastro-oesophageal cancer patients |
title_sort | cell-free tumour dna analysis detects copy number alterations in gastro-oesophageal cancer patients |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861431/ https://www.ncbi.nlm.nih.gov/pubmed/33539436 http://dx.doi.org/10.1371/journal.pone.0245488 |
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