scholarly journals Tissue-specific cell-free DNA degradation quantifies circulating tumor DNA burden

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Guanhua Zhu ◽  
Yu A. Guo ◽  
Danliang Ho ◽  
Polly Poon ◽  
Zhong Wee Poh ◽  
...  
Keyword(s):  
Disease Progression ◽  
Cancer Patients ◽  
Circulating Tumor Dna ◽  
Specific Cell ◽  
Regulatory Regions ◽  
Cell Free Dna ◽  
Invasive Approach ◽  
Tissue Specific ◽  
Free Dna ◽  
Tumor Dna

AbstractProfiling of circulating tumor DNA (ctDNA) may offer a non-invasive approach to monitor disease progression. Here, we develop a quantitative method, exploiting local tissue-specific cell-free DNA (cfDNA) degradation patterns, that accurately estimates ctDNA burden independent of genomic aberrations. Nucleosome-dependent cfDNA degradation at promoters and first exon-intron junctions is strongly associated with differential transcriptional activity in tumors and blood. A quantitative model, based on just 6 regulatory regions, could accurately predict ctDNA levels in colorectal cancer patients. Strikingly, a model restricted to blood-specific regulatory regions could predict ctDNA levels across both colorectal and breast cancer patients. Using compact targeted sequencing (<25 kb) of predictive regions, we demonstrate how the approach could enable quantitative low-cost tracking of ctDNA dynamics and disease progression.

scholarly journals Detection of Circulating Tumor DNA in Patients With Leiomyosarcoma With Progressive Disease

2019 ◽  
pp. 1-11 ◽  
Author(s):  
Matthew L. Hemming ◽  
Kelly Klega ◽  
Justin Rhoades ◽  
Gavin Ha ◽  
Kate E. Acker ◽  
...  
Keyword(s):  
Disease Progression ◽  
Tumor Size ◽  
Disease Burden ◽  
Progressive Disease ◽  
Circulating Tumor Dna ◽  
Tumor Burden ◽  
Blood Draw ◽  
Cell Free Dna ◽  
Free Dna ◽  
Tumor Dna

Purpose Leiomyosarcoma (LMS) is a soft-tissue sarcoma characterized by multiple copy number alterations (CNAs) and without common recurrent single-nucleotide variants. We evaluated the feasibility of detecting circulating tumor DNA (ctDNA) with next-generation sequencing in a cohort of patients with LMS whose tumor burden ranged from no evidence of disease to metastatic progressive disease. Patients and Methods We evaluated cell-free DNA in plasma samples and paired genomic DNA from resected tumors from patients with LMS by ultra-low passage whole-genome sequencing. Sequencing reads were aligned to the human genome and CNAs that were identified in cell-free DNA and tumor DNA by ichorCNA software to determine the presence of ctDNA. Clinical data were reviewed to assess disease burden and clinicopathologic features. Results We identified LMS ctDNA in 11 (69%) of 16 patients with disease progression and total tumor burden greater than 5 cm. Sixteen patients with stable disease or low disease burden at the time of blood draw were found to have no detectable ctDNA. Higher ctDNA fraction of total cell-free DNA was associated with increasing tumor size and disease progression. Conserved CNAs were found between primary tumors and ctDNA in each case, and recurrent CNAs were found across LMS samples. ctDNA levels declined after resection of progressive disease in one case and became detectable upon disease relapse in another individual patient. Conclusion These results suggest that ctDNA, assayed by a widely available sequencing approach, may be useful as a biomarker for a subset of patients with uterine and extrauterine LMS. Higher levels of ctDNA correlate with tumor size and disease progression. Liquid biopsies may assist in guiding treatment decisions, monitoring response to systemic therapy, surveying for disease recurrence, and differentiating benign and malignant smooth muscle tumors.

scholarly journals Can Circulating Cell-Free DNA or Circulating Tumor DNA Be a Promising Marker in Ovarian Cancer?

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Ming Yu ◽  
Yu Zhu ◽  
Lichen Teng ◽  
Jialin Cui ◽  
Yajuan Su
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Circulating Tumor Dna ◽  
Early Screening ◽  
Cell Free Dna ◽  
Diagnosis And Prognosis ◽  
Free Dna ◽  
Wide Range ◽  
Tumor Dna ◽  
Circulating Cell Free Dna

In recent years, the studies on ovarian cancer have made great progress, but the morbidity and mortality of patients with ovarian cancer are still very high. Due to the lack of effective early screening and detecting tools, 70% of ovarian cancer patients are diagnosed at an advanced stage. The overall survival rate of ovarian cancer patients treated with surgical combined with chemotherapy has not been significantly improved, and they usually relapse or resist chemotherapy. Therefore, a novel tumor marker is beneficial for the diagnosis and prognosis of patients with ovarian cancer. As the index of “liquid biopsy,” circulating cell-free DNA/circulating tumor DNA (cfDNA/ctDNA) has attracted a lot of attention. It has more remarkable advantages than traditional methods and gives a wide range of clinical applications in kinds of solid tumors. This review attempts to illuminate the important value of cfDNA/ctDNA in ovarian cancer, including diagnosis, monitoring, and prognosis. Meanwhile, we will present future directions and challenges for detection of cfDNA/ctDNA.

Plasma cell-free DNA and fraction of circulating KRAS mutations as prognostic in patients with metastatic colorectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 490-490 ◽  
Author(s):  
David Sefrioui ◽  
Nasrin Vasseur ◽  
Richard Sesboüé ◽  
France Blanchard ◽  
Alice Oden-Gangloff ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Plasma Cell ◽  
Circulating Tumor Dna ◽  
Dna Fragments ◽  
Wild Type ◽  
Kras Mutations ◽  
Cell Free Dna ◽  
Free Dna ◽  
Tumor Dna

490 Background: It has been suggested that detection of circulating tumor DNA may be relevant in patients with metastatic colorectal cancer (mCRC). The main objective of the present study was to evaluate a method based on the TaqMan Mutation Detection Assay (TMDA) for the detection of circulating KRAS mutations in mCRC patients. Moreover, we also investigated the prognostic impact of the plasma cell-free DNA and the fraction of circulating KRAS mutations. Methods: The study was conducted from April to July 2013 and plasma samples were prospectively collected in a series of 35 mCRC patients treated with chemotherapy (CT). QIAamp Circulating Nucleic Acid kit was used for DNA extraction and Quant-iT High Sensitivity dsDNA Assay for cf-DNA quantification. Detection of circulating tumor DNA was based on the KRAS mutations detected in tumour and was performed in plasma by the castPCR Technology TMDA. Response to CT was assessed according to RECIST criteria. The results of plasma cf-DNA and level of mutant DNA fragments were correlated with response and 3-months survival. Results: We isolated and quantified plasma cf-DNA in all patients with a mean concentration of 106 ng/mL. Among them, 18 were wild-type and 17 mutated for KRAS in the tumour. Detection of circulating KRAS mutations was performed with TMDA in 23 patients (10 KRAS wild-type and 13 KRAS mutated). The sensitivity was 62% (8/13) and specificity 100% (0/10) with a level of circulating mutant DNA fragments ranging from 0 to 29%. Plasma cf-DNA and level of circulating mutant DNA were both significantly correlated with the 3-months survival (mean 36 versus 524 ng/mL, p=0.0015 and 2% versus 29%, p<0.0001). There was a non significant trend for response to CT (respectively p=0.14 and p=0.12). Conclusions: TMDA method is a simple, accurate and non-invasive tool for the detection of circulating tumor DNA. Our preliminary results also suggest that plasma cf-DNA and fraction of mutant DNA fragments could be prognostic markers in mCRC patients.

scholarly journals Circulating Cell-Free DNA or Circulating Tumor DNA in the Management of Ovarian and Endometrial Cancer

2019 ◽  
Vol Volume 12 ◽  
pp. 11517-11530 ◽  
Author(s):  
Qian Chen ◽  
Zi-Han Zhang ◽  
Shu Wang ◽  
Jing-He Lang
Keyword(s):  
Endometrial Cancer ◽  
Circulating Tumor Dna ◽  
Cell Free Dna ◽  
Free Dna ◽  
Tumor Dna ◽  
Circulating Cell Free Dna
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