scholarly journals False positive cell free DNA screening for microdeletions due to non-pathogenic copy number variants

2016 ◽  
Vol 36 (6) ◽  
pp. 584-586 ◽  
Author(s):  
Cheryl A. Mather ◽  
Zhongxia Qi ◽  
Arun P. Wiita
Keyword(s):  
False Positive ◽  
Copy Number ◽  
Copy Number Variants ◽  
Cell Free Dna ◽  
Free Dna

scholarly journals Detection of Clonal and Subclonal Copy-Number Variants in Cell-Free DNA from Patients with Breast Cancer Using a Massively Multiplexed PCR Methodology

2015 ◽  
Vol 8 (5) ◽  
pp. 407-416 ◽  
Author(s):  
Eser Kirkizlar ◽  
Bernhard Zimmermann ◽  
Tudor Constantin ◽  
Ryan Swenerton ◽  
Bin Hoang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Copy Number ◽  
Copy Number Variants ◽  
Cell Free Dna ◽  
Multiplexed Pcr ◽  
Free Dna

scholarly journals Genome-wide cell-free DNA screening: a focus on copy-number variants

2021 ◽  
Author(s):  
Jill Rafalko ◽  
Erica Soster ◽  
Samantha Caldwell ◽  
Eyad Almasri ◽  
Thomas Westover ◽  
...  
Keyword(s):  
Copy Number ◽  
Chromosomal Abnormalities ◽  
Diagnostic Testing ◽  
Copy Number Variants ◽  
Cell Free Dna ◽  
Predictive Values ◽  
Free Dna ◽  
Genome Wide ◽  
Cfdna Screening ◽  
Diagnostic Outcomes

Abstract Purpose Of 86,902 prenatal genome-wide cell-free DNA (cfDNA) screening tests, 4,121 were positive for a chromosome abnormality. This study examines 490 cases screen-positive for one or more subchromosomal copy-number variants (CNV) from genome-wide cfDNA screening. Methods Cases positive for one or more subchromosomal CNV from genome-wide cfDNA screening and diagnostic outcomes were compiled. Diagnostic testing trends were analyzed, positive predictive values (PPVs) were calculated, and the type of chromosomal abnormalities ultimately confirmed by diagnostic testing were described. Results CNVs were identified in 0.56% of screened specimens. Of the 490 cases screen-positive for one or more CNV, diagnostic outcomes were available for 244 cases (50%). The overall PPV among the cases with diagnostic outcomes was 74.2% (95% CI: 68.1–79.5%) and 71.8% (95% CI: 65.5–77.4%) for “fetal-only” events. Overall, isolated CNVs showed a lower PPV of 61.0% (95% CI: 52.5–68.8%) compared to complex CNVs at 93.9% (95% CI: 86.6–97.5%). Isolated deletions/duplications and unbalanced structural rearrangements were the most common diagnostic outcomes when isolated and complex CNVs were identified by cfDNA screening, respectively. Conclusion Genome-wide cfDNA screening identifies chromosomal abnormalities beyond the scope of traditional cfDNA screening, and the overall PPV associated with subchromosomal CNVs in cases with diagnostic outcomes was >70%.

scholarly journals A novel decision tree model based on chromosome imbalances in cell-free DNA and CA-125 in the differential diagnosis of ovarian cancer

2021 ◽  
pp. 172460082199235
Author(s):  
Weina Zhang ◽  
Yu-min Zhang ◽  
Yuan Gao ◽  
Shengmiao Zhang ◽  
Weixin Chu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Differential Diagnosis ◽  
Decision Tree ◽  
Copy Number ◽  
Malignant Tumors ◽  
Copy Number Variations ◽  
Ca 125 ◽  
Benign Tumors ◽  
Cell Free Dna ◽  
Free Dna

Objective: CA-125 is widely used as biomarker of ovarian cancer. However, CA-125 suffers low accuracy. We developed a hybrid analytical model, the Ovarian Cancer Decision Tree (OCDT), employing a two-layer decision tree, which considers genetic alteration information from cell-free DNA along with CA-125 value to distinguish malignant tumors from benign tumors. Methods: We consider major copy number alterations at whole chromosome and chromosome-arm level as the main feature of our detection model. Fifty-eight patients diagnosed with malignant tumors, 66 with borderline tumors, and 10 with benign tumors were enrolled. Results: Genetic analysis revealed significant arm-level imbalances in most malignant tumors, especially in high-grade serous cancers in which 12 chromosome arms with significant aneuploidy ( P<0.01) were identified, including 7 arms with significant gains and 5 with significant losses. The area under receiver operating characteristic curve (AUC) was 0.8985 for copy number variations analysis, compared to 0.8751 of CA125. The OCDT was generated with a cancerous score (CScore) threshold of 5.18 for the first level, and a CA-125 value of 103.1 for the second level. Our most optimized OCDT model achieved an AUC of 0.975. Conclusions: The results suggested that genetic variations extracted from cfDNA can be combined with CA-125, and together improved the differential diagnosis of malignant from benign ovarian tumors. The model would aid in the pre-operative assessment of women with adnexal masses. Future clinical trials need to be conducted to further evaluate the value of CScore in clinical settings and search for the optimal threshold for malignancy detection.

Circulating Janus kinase family DNA levels in psoriasis: elevated JAK2 DNA copy number in cell‐free DNA

2021 ◽  
Author(s):  
Kayo Kashiwada‐Nakamura ◽  
Tselmeg Mijiddorj Myangat ◽  
Ikko Kajihara ◽  
Hisashi Kanemaru ◽  
Soichiro Sawamura ◽  
...  
Keyword(s):  
Copy Number ◽  
Janus Kinase ◽  
Dna Copy Number ◽  
Cell Free Dna ◽  
Free Dna ◽  
Kinase Family

Cell-free DNA profiling in patients with lupus nephritis

Lupus ◽  
2020 ◽  
Vol 29 (13) ◽  
pp. 1759-1772
Author(s):  
Anna Truszewska ◽  
Agnieszka Wirkowska ◽  
Kamila Gala ◽  
Piotr Truszewski ◽  
Łucja Krzemień-Ojak ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Copy Number ◽  
Severe Disease ◽  
Renal Involvement ◽  
Mtdna Copy Number ◽  
Cell Free Dna ◽  
Free Dna ◽  
Mitochondrial Fractions ◽  
Kidney Involvement

Background Increased level of cell-free DNA (cf-DNA) is associated with systemic lupus erythematosus (SLE) and might be related to disease activity. The aim of this study was to evaluate whether cfDNA integrity, size distribution and concentration of different cfDNA fractions is associated with lupus activity and kidney involvement. Methods Blood samples were collected from 43 SLE patients and 50 healthy controls. Nuclear and mitochondrial fractions of cfDNA and intracellular DNA were quantified by real-time qPCR. Sizing and quantification of total cfDNA level was performed on Bioanalyzer. Results We determined four parameters that characterized cfDNA profile: fragmentation index, ratio of intra- to extracellular mtDNA copy number, cfDNA concentration, and presence of 54–149 bp and 209–297 bp fragments. Patients with healthy-like cfDNA profile had higher eGFR ( P = 0.009) and more often no indications for kidney biopsy or less advanced lupus nephritis (LN) ( P = 0.037). In contrary, SLE patients with distinct cfDNA profile (characterized by increased cfDNA concentration and fragmentation, higher discrepancy between intra- to extracellular mtDNA copy number, and the presence of 54–149 bp and 209–297 bp fragments) had lower eGFR ( P = 0.005) and more often advanced LN or history of renal transplantation ( P = 0.001). Conclusions We showed that cfDNA profiling may help to distinguish SLE patients with renal involvement and severe disease course from patients with more favorable outcomes. We suggest cfDNA profile a promising SLE biomarker.

scholarly journals Genome-Wide Analysis of Circulating Cell-Free DNA Copy Number Detects Active Melanoma and Predicts Survival

2018 ◽  
Vol 64 (9) ◽  
pp. 1338-1346 ◽  
Author(s):  
Shobha Silva ◽  
Sarah Danson ◽  
Dawn Teare ◽  
Fiona Taylor ◽  
James Bradford ◽  
...  
Keyword(s):  
Copy Number ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Dna Copy Number ◽  
Cell Free Dna ◽  
Free Dna ◽  
Potential Biomarker ◽  
Melanoma Patients ◽  
Active Disease ◽  
Circulating Cell Free Dna

Abstract BACKGROUND A substantial number of melanoma patients develop local or metastatic recurrence, and early detection of these is vital to maximise benefit from new therapies such as inhibitors of BRAF and MEK, or immune checkpoints. This study explored the use of novel DNA copy-number profiles in circulating cell-free DNA (cfDNA) as a potential biomarker of active disease and survival. PATIENTS AND METHODS Melanoma patients were recruited from oncology and dermatology clinics in Sheffield, UK, and cfDNA was isolated from stored blood plasma. Using low-coverage whole-genome sequencing, we created copy-number profiles from cfDNA from 83 melanoma patients, 44 of whom had active disease. We used scoring algorithms to summarize copy-number aberrations and investigated their utility in multivariable logistic and Cox regression analyses. RESULTS The copy-number aberration score (CNAS) was a good discriminator of active disease (odds ratio, 3.1; 95% CI, 1.5–6.2; P = 0.002), and CNAS above or below the 75th percentile remained a significant discriminator in multivariable analysis for active disease (P = 0.019, with area under ROC curve of 0.90). Additionally, mortality was higher in those with CNASs above the 75th percentile than in those with lower scores (HR, 3.4; 95% CI, 1.5–7.9; P = 0.005), adjusting for stage of disease, disease status (active or resected), BRAF status, and cfDNA concentration. CONCLUSIONS This study demonstrates the potential of a de novo approach utilizing copy-number profiling of cfDNA as a biomarker of active disease and survival in melanoma. Longitudinal analysis of copy-number profiles as an early marker of relapsed disease is warranted.

Abstract 3138: Changes in tumor cell-free DNA copy number instability (CNI) predict therapeutic response in metastatic cancers

2016 ◽  
Author(s):  
Glen J. Weiss ◽  
Julia Beck ◽  
Donald P. Braun ◽  
Kirsten Bornemann-Kolatzki ◽  
Heather Barilla ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Copy Number ◽  
Therapeutic Response ◽  
Dna Copy Number ◽  
Cell Free Dna ◽  
Free Dna

scholarly journals Urothelial Carcinoma Detection Based on Copy Number Profiles of Urinary Cell-Free DNA by Shallow Whole-Genome Sequencing

2019 ◽  
Vol 66 (1) ◽  
pp. 188-198 ◽  
Author(s):  
Guangzhe Ge ◽  
Ding Peng ◽  
Bao Guan ◽  
Yuanyuan Zhou ◽  
Yanqing Gong ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Genome Sequencing ◽  
Copy Number ◽  
Support Vector ◽  
Sequencing Data ◽  
Validation Data ◽  
Data Set ◽  
Cell Free Dna ◽  
Clinical Sensitivity ◽  
Free Dna

Abstract BACKGROUND Current noninvasive assays for urothelial carcinoma (UC) lack clinical sensitivity and specificity. Given the utility of plasma cell-free DNA (cfDNA) biomarkers, the development of urinary cfDNA biomarkers may improve the diagnostic sensitivity. METHODS We assessed copy number alterations (CNAs) by shallow genome-wide sequencing of urinary cfDNA in 95 cancer-free individuals and 65 patients with UC, 58 with kidney cancer, and 45 with prostate cancer. We used a support vector machine to develop a diagnostic classifier based on CNA profiles to detect UC (UCdetector). The model was further validated in an independent cohort (52 patients). Genome sequencing data of tumor specimens from 90 upper tract urothelial cancers (UTUCs) and CNA data for 410 urothelial carcinomas of bladder (UCBs) from The Cancer Genome Atlas were used to validate the classifier. Genome sequencing data for urine sediment from 32 patients with UC were compared with cfDNA. To monitor the treatment efficacy, we collected cfDNA from 7 posttreatment patients. RESULTS Urinary cfDNA was a more sensitive alternative to urinary sediment. The UCdetector could detect UC at a median clinical sensitivity of 86.5% and specificity of 94.7%. UCdetector performed well in an independent validation data set. Notably, the CNA features selected by UCdetector were specific markers for both UTUC and UCB. Moreover, CNA changes in cfDNA were consistent with the treatment effects. Meanwhile, the same strategy could localize genitourinary cancers to tissue of origin in 70.1% of patients. CONCLUSIONS Our findings underscore the potential utility of urinary cfDNA CNA profiles as a basis for noninvasive UC detection and surveillance.

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