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

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.

Baseline mutation profiling of circulating cell-free DNA from healthy individuals to improve the detection accuracy of circulating tumor DNA in cancers.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23057-e23057
Author(s):  
Geng Tian ◽  
Ligang Xia ◽  
Zhoufang Li ◽  
Xiaohua Li ◽  
Feiyue Xu ◽  
...  
Keyword(s):  
Genomic Dna ◽  
Circulating Tumor Dna ◽  
Clinical Diagnostics ◽  
Detection Accuracy ◽  
Healthy Individuals ◽  
Cell Free Dna ◽  
Free Dna ◽  
Tumor Dna ◽  
Mutation Profiling ◽  
Circulating Cell Free Dna

e23057 Background: Cell-free circulating tumor DNA (ctDNA) has emerged as an effective blood-based biomarker for clinical diagnostics in cancers, improving the accuracy and efficiency of cancer treatment for clinic. However, the somatic mutations originated from inheritance or normal biological metabolism in circulating cell-free DNA (cfDNA) in plasma can largely interfere with the detection of ctDNA. The baseline for ctDNA evaluation is urgently needed for accuracy identification of ctDNAs in patients. Methods: Averagely 20 ml blood samples were collected from more than 1200 individuals including healthy volunteers, lung cancer, colorectal cancer, pancreatic cancer, gastric cancer patients, etc. Genomic DNA from white blood cells and cfDNA from plasma were extracted and constructed as sequencing libraries using a panel contains 50 cancer-associated genes, respectively for each sample. Then they are subjected to ultra-deep sequencing with average depth > 40000 folds covering ~21K nucleotide regions. Results: The background somatic mutation frequencies were detected in genomic DNA and cfDNA in healthy controls. The results showed that most of mutations in cfDNA were consistent with those in genomic DNA. Using data from 1200 individuals, we generated the baseline mutation profiling of cfDNA, which was referred in the ctDNA determination in cancer samples, which significantly improved the accuracy of ctDNA detection compared with tissue biopsy. Conclusions: Our studies demonstrated the importance of sequencing both cfDNA and genomic DNA for ctDNA detection in cancers. We also determined the baseline mutation profiling of circulating cfDNA from more than 1200 healthy individuals and confirmed the value of it by comparing with DNA sequencing data in cancer tissue. Our work offers clue on how to improve the detection accuracy of circulating tumor DNA in early cancer diagnosis.

scholarly journals The Early Diagnosis in Lung Cancer by the Detection of Circulating Tumor DNA

2017 ◽  
Author(s):  
Geng Tian ◽  
Xiaohua Li ◽  
Yuancai Xie ◽  
Feiyue Xu ◽  
Dan Yu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Genomic Dna ◽  
Tumor Tissue ◽  
Circulating Tumor Dna ◽  
Driver Genes ◽  
Cell Free Dna ◽  
Lung Cancer Patients ◽  
Free Dna ◽  
Tumor Dna ◽  
Circulating Cell Free Dna

BackgroundRemarkable advances for clinical diagnosis and treatment in cancers including lung cancer involve cell-free circulating tumor DNA (ctDNA) detection through next generation sequencing. However, before the sensitivity and specificity of ctDNA detection can be widely recognized, the consistency of mutations in tumor tissue and ctDNA should be evaluated. The urgency of this consistency is extremely obvious in lung cancer to which great attention has been paid to in liquid biopsy field.MethodsWe have developed an approach named systematic error correction sequencing (Sec-Seq) to improve the evaluation of sequence alterations in circulating cell-free DNA. Averagely 10 ml preoperative blood samples were collected from 30 patients containing pulmonary space occupying pathological changes by traditional clinic diagnosis. cfDNA from plasma, genomic DNA from white blood cells, and genomic DNA from solid tumor of above patients were extracted and constructed as libraries for each sample before subjected to sequencing by a panel contains 50 cancer-associated genes encompassing 29 kb by custom probe hybridization capture with average depth >40000, 7000, or 6300 folds respectively.ResultsDetection limit for mutant allele frequency in our study was 0.1%. The sequencing results were analyzed by bioinformatic expertise based on our previous studies on the baseline mutation profiling of circulating cell-free DNA and the clinicopathological data of these patients. Among all the lung cancer patients, 78% patients were predicted as positive by ctDNA sequencing when the shreshold was defined as at least one of the hotspot mutations detected in the blood (ctDNA) was also detected in tumor tissue. Pneumonia and pulmonary tuberculosis were detected as negative according to the above standard. When evaluating all hotspots in driver genes in the panel, 24% mutations detected in tumor tissue (tDNA) were also detected in patients blood (ctDNA). When evaluating all genetic variations in the panel, including all the driver genes and passenger genes, 28% detected in tumor tissue (tDNA) were also detected in patients blood (ctDNA). Positive detection rates of plasma ctDNA in stage I lung cancer patients is 85%, compared with 17% of tumor biomarkers.ConclusionWe demonstrated the importance of sequencing both circulating cell-free DNA and genomic DNA in tumor tissue for ctDNA detection in lung cancer currently. We also determined and confirmed the consistency of ctDNA and tumor tissue through NGS according to the criteria explored in our studies. Our strategy can initially distinguish the lung cancer from benign lesions of lung. Our work shows that the consistency will be benefited from the optimization in sensitivity and specificity in ctDNA detection.

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.

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 Clinical correlates of circulating cell-free DNA tumor fraction

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256436
Author(s):  
Joerg Bredno ◽  
Jafi Lipson ◽  
Oliver Venn ◽  
Alexander M. Aravanis ◽  
Arash Jamshidi
Keyword(s):  
Colorectal Cancer ◽  
Early Detection ◽  
Metabolic Activity ◽  
Linear Models ◽  
Circulating Tumor Dna ◽  
Cell Free Dna ◽  
Clinical Correlates ◽  
Cancer Early Detection ◽  
Free Dna ◽  
Tumor Dna

Background Oncology applications of cell-free DNA analysis are often limited by the amount of circulating tumor DNA and the fraction of cell-free DNA derived from tumor cells in a blood sample. This circulating tumor fraction varies widely between individuals and cancer types. Clinical factors that influence tumor fraction have not been completely elucidated. Methods and findings Circulating tumor fraction was determined for breast, lung, and colorectal cancer participant samples in the first substudy of the Circulating Cell-free Genome Atlas study (CCGA; NCT02889978; multi-cancer early detection test development) and was related to tumor and patient characteristics. Linear models were created to determine the influence of tumor size combined with mitotic or metabolic activity (as tumor mitotic volume or excessive lesion glycolysis, respectively), histologic type, histologic grade, and lymph node status on tumor fraction. For breast and lung cancer, tumor mitotic volume and excessive lesion glycolysis (primary lesion volume scaled by percentage positive for Ki-67 or PET standardized uptake value minus 1.0, respectively) were the only statistically significant covariates. For colorectal cancer, the surface area of tumors invading beyond the subserosa was the only significant covariate. The models were validated with cases from the second CCGA substudy and show that these clinical correlates of circulating tumor fraction can predict and explain the performance of a multi-cancer early detection test. Conclusions Prognostic clinical variables, including mitotic or metabolic activity and depth of invasion, were identified as correlates of circulating tumor DNA by linear models that relate clinical covariates to tumor fraction. The identified correlates indicate that faster growing tumors have higher tumor fractions. Early cancer detection from assays that analyze cell-free DNA is determined by circulating tumor fraction. Results support that early detection is particularly sensitive for faster growing, aggressive tumors with high mortality, many of which have no available screening today.

Aberrant Telomere Length in Circulating Cell-Free DNA as Possible Blood Biomarker with High Diagnostic Performance in Endometrial Cancer

2020 ◽  
Vol 26 (4) ◽  
pp. 2281-2289 ◽  
Author(s):  
Marco Benati ◽  
Martina Montagnana ◽  
Elisa Danese ◽  
Martina Mazzon ◽  
Elisa Paviati ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Telomere Length ◽  
Diagnostic Performance ◽  
Cell Free Dna ◽  
Blood Biomarker ◽  
Free Dna ◽  
Circulating Cell Free Dna
Sign in / Sign up

Export Citation Format

Share Document