scholarly journals Non-invasive prenatal testing for fetal chromosomal abnormalities by low-coverage whole-genome sequencing of maternal plasma DNA: review of 1982 consecutive cases in a single center

2014 ◽  
Vol 43 (3) ◽  
pp. 254-264 ◽  
Author(s):  
T. K. Lau ◽  
S. W. Cheung ◽  
P. S. S. Lo ◽  
A. N. Pursley ◽  
M. K. Chan ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Chromosomal Abnormalities ◽  
Prenatal Testing ◽  
Maternal Plasma ◽  
Whole Genome ◽  
Single Center ◽  
Plasma Dna ◽  
Non Invasive ◽  
Low Coverage

scholarly journals Cell-free tumour DNA analysis detects copy number alterations in gastro-oesophageal cancer patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0245488
Author(s):  
Karin Wallander ◽  
Jesper Eisfeldt ◽  
Mats Lindblad ◽  
Daniel Nilsson ◽  
Kenny Billiau ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Oesophageal Cancer ◽  
Copy Number ◽  
Dna Analysis ◽  
Tissue Sample ◽  
Whole Genome ◽  
Copy Number Alterations ◽  
Plasma Dna ◽  
Low Coverage

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.

Isolation and whole genome sequencing of fetal cells from maternal blood towards the ultimate non-invasive prenatal testing

2017 ◽  
Vol 37 (13) ◽  
pp. 1311-1321 ◽  
Author(s):  
Fang Chen ◽  
Ping Liu ◽  
Ying Gu ◽  
Zhu Zhu ◽  
Amulya Nanisetti ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Prenatal Testing ◽  
Maternal Blood ◽  
Whole Genome ◽  
Fetal Cells ◽  
Non Invasive

scholarly journals Secondary findings from non-invasive prenatal testing for common fetal aneuploidies by whole genome sequencing as a clinical service

2013 ◽  
Vol 33 (6) ◽  
pp. 602-608 ◽  
Author(s):  
Tze Kin Lau ◽  
Fu Man Jiang ◽  
Robert J. Stevenson ◽  
Tsz Kin Lo ◽  
Lin Wai Chan ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Prenatal Testing ◽  
Clinical Service ◽  
Whole Genome ◽  
Secondary Findings ◽  
Non Invasive ◽  
Fetal Aneuploidies

scholarly journals Pilot Screening of Cell-Free mtDNA in NIPT: Quality Control, Variant Calling, and Haplogroup Determination

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 743
Author(s):  
Alisa Morshneva ◽  
Polina Kozyulina ◽  
Elena Vashukova ◽  
Olga Tarasenko ◽  
Natalia Dvoynova ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Variant Calling ◽  
Prenatal Testing ◽  
Large Data ◽  
Large Data Sets ◽  
Data Sets ◽  
Whole Genome ◽  
Clinical Tests ◽  
Non Invasive

Clinical tests based on whole-genome sequencing are generally focused on a single task approach, testing one or several parameters, although whole-genome sequencing (WGS) provides us with large data sets that can be used for many supportive analyses. In spite of low genome coverage, data of WGS-based non-invasive prenatal testing (NIPT) contain fully sequenced mitochondrial DNA (mtDNA). This mtDNA can be used for variant calling, ancestry analysis, population studies and other approaches that extend NIPT functionality. In this study, we analyse mtDNA pool from 645 cell-free DNA (cfDNA) samples of pregnant women from different regions of Russia, explore the effects of transportation and storing conditions on mtDNA content, analyse effects, frequency and location of mitochondrial variants called from samples and perform haplogroup analysis, revealing the most common mitochondrial superclades. We have shown that, despite the relatively low sequencing depth of unamplified mtDNA from cfDNA samples, the mtDNA analysis in these samples is still an informative instrument suitable for research and screening purposes.

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

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14523-e14523
Author(s):  
Bella Hai Nguyen ◽  
Nick Wong ◽  
Timothy Semple ◽  
Olivia Ruhen ◽  
Stephen Q Wong ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Metastatic Cancer ◽  
Valuable Insight ◽  
Whole Genome ◽  
Plasma Dna ◽  
Primary Tumors ◽  
Hpv Status ◽  
Ffpe Samples ◽  
Low Coverage

e14523 Background: Low-coverage whole genome sequencing (LC-WGS) of tumors provides valuable insight into molecular changes driving oncogenesis. A novel liquid biopsy source of tumor DNA for analysis is from extracellular vesicles (EV) obtained from blood. This study compared copy number alteration (CNA) profiles generated from LC-WGS of Formalin-Fixed Paraffin-Embedded (FFPE) DNA and EV-associated DNA in cancer patients. Methods: Three metastatic base of tongue (BOT), two of which were Human Papillomavirus-related (HPV+) and two metastatic cutaneous squamous cell carcinoma (cSCC) patients were included. EV were isolated using ultracentrifugation from patients’ plasma. DNA was extracted from FFPE tumor tissue and EV. LC-WGS aiming for 0.5-1X coverage was performed using a validated method. CNA profiles were generated using the QDNAseq package, with gains defined as a log2 ratio ≥0.15 and losses < -0.15. Results: CNA profiles of FFPE samples from BOT patients demonstrated significant variation regardless of HPV status, with a mean of 20 regions containing 125 CNA (amplifications or deletions) per sample. The cSCC FFPE samples demonstrated a mean of 23 regions containing 189 CNA per sample. Overall, EV-associated DNA CNA profiles had limited similarity with primary FFPE. EV-associated DNA showed a lower number of CNA regions and CNA, with a mean of 3.7 CNA regions and 11.4 CNA for BOT samples and 6.5 regions and 15.9 CNA for cSCC samples. The HPV-BOT sample showed 2/3 EV-CNA regions matched corresponding FFPE-CNA profile (n = 15). The two HPV+ samples were less consistent with only 1/3 and 1/5 EV-CNA regions matching FFPE-CNA profiles (n = 39 and n = 6, respectively). The two cSCC cases showed more consistency with 4/6 and 6/7 EV-CNA regions matching FFPE-CNA profiles (n = 21 and n = 25, respectively). In the matched CNA regions, the mean CNA in EV-associated DNA was 7.5 and in FFPE-DNA was 97. Conclusions: Although selected EV-associated DNA CNA regions reflected the primary tumors, these were limited in number and did not globally reflect the FFPE derived CNA profiles.

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