scholarly journals Accurate detection of circulating tumor DNA using nanopore consensus sequencing

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Alessio Marcozzi ◽  
Myrthe Jager ◽  
Martin Elferink ◽  
Roy Straver ◽  
Joost H. van Ginkel ◽  
...  
Keyword(s):  
Circulating Tumor Dna ◽  
Tumor Burden ◽  
Liquid Biopsies ◽  
Genomic Locus ◽  
Base Calling ◽  
Accurate Detection ◽  
Tumor Diagnostics ◽  
Oxford Nanopore ◽  
A New Technique ◽  
Tumor Dna

AbstractLevels of circulating tumor DNA (ctDNA) in liquid biopsies may serve as a sensitive biomarker for real-time, minimally-invasive tumor diagnostics and monitoring. However, detecting ctDNA is challenging, as much fewer than 5% of the cell-free DNA in the blood typically originates from the tumor. To detect lowly abundant ctDNA molecules based on somatic variants, extremely sensitive sequencing methods are required. Here, we describe a new technique, CyclomicsSeq, which is based on Oxford Nanopore sequencing of concatenated copies of a single DNA molecule. Consensus calling of the DNA copies increased the base-calling accuracy ~60×, enabling accurate detection of TP53 mutations at frequencies down to 0.02%. We demonstrate that a TP53-specific CyclomicsSeq assay can be successfully used to monitor tumor burden during treatment for head-and-neck cancer patients. CyclomicsSeq can be applied to any genomic locus and offers an accurate diagnostic liquid biopsy approach that can be implemented in clinical workflows.

scholarly journals Accurate detection of circulating tumor DNA using nanopore consensus sequencing

2020 ◽  
Author(s):  
Alessio Marcozzi ◽  
Myrthe Jager ◽  
Martin Elferink ◽  
Roy Straver ◽  
Joost H. van Ginkel ◽  
...  
Keyword(s):  
Point Of Care ◽  
Circulating Tumor Dna ◽  
Tumor Burden ◽  
Liquid Biopsies ◽  
Genomic Locus ◽  
Base Calling ◽  
Accurate Detection ◽  
Tumor Diagnostics ◽  
A New Technique ◽  
Tumor Dna

ABSTRACTLevels of circulating tumor DNA (ctDNA) in liquid biopsies may serve as a sensitive biomarker for real-time, minimally-invasive tumor diagnostics and monitoring. However, detecting ctDNA is challenging, as much fewer than 5% of the cell-free DNA in the blood typically originates from the tumor. To detect lowly abundant ctDNA molecules based on somatic variants, extremely sensitive sequencing methods are required. Here, we describe a new technique, CyclomicsSeq, which is based on Oxford Nanopore sequencing of concatenated copies of a single DNA molecule. Consensus calling of the DNA copies increased the base-calling accuracy ∼60x, enabling accurate detection of TP53 mutations at frequencies down to 0.02%. We demonstrate that a TP53-specific CyclomicsSeq assay can be successfully used to monitor tumor burden during treatment for head-and-neck cancer patients. CyclomicsSeq can be applied to any genomic locus and offers an accurate diagnostic liquid biopsy approach that can be implemented in point-of-care clinical workflows.

scholarly journals Clinical utility of circulating tumor DNA as a response and follow-up marker in cancer therapy

2020 ◽  
Vol 39 (3) ◽  
pp. 999-1013 ◽  
Author(s):  
Pieter A. Boonstra ◽  
Thijs T. Wind ◽  
Michel van Kruchten ◽  
Ed Schuuring ◽  
Geke A. P. Hospers ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Treatment Response ◽  
Clinical Utility ◽  
Tumor Response ◽  
Circulating Tumor Dna ◽  
Tumor Burden ◽  
Liquid Biopsies ◽  
Secondary Resistance ◽  
Tumor Dna

Abstract Response evaluation for cancer treatment consists primarily of clinical and radiological assessments. In addition, a limited number of serum biomarkers that assess treatment response are available for a small subset of malignancies. Through recent technological innovations, new methods for measuring tumor burden and treatment response are becoming available. By utilization of highly sensitive techniques, tumor-specific mutations in circulating DNA can be detected and circulating tumor DNA (ctDNA) can be quantified. These so-called liquid biopsies provide both molecular information about the genomic composition of the tumor and opportunities to evaluate tumor response during therapy. Quantification of tumor-specific mutations in plasma correlates well with tumor burden. Moreover, with liquid biopsies, it is also possible to detect mutations causing secondary resistance during treatment. This review focuses on the clinical utility of ctDNA as a response and follow-up marker in patients with non-small cell lung cancer, melanoma, colorectal cancer, and breast cancer. Relevant studies were retrieved from a literature search using PubMed database. An overview of the available literature is provided and the relevance of ctDNA as a response marker in anti-cancer therapy for clinical practice is discussed. We conclude that the use of plasma-derived ctDNA is a promising tool for treatment decision-making based on predictive testing, detection of resistance mechanisms, and monitoring tumor response. Necessary steps for translation to daily practice and future perspectives are discussed.

scholarly journals Prognostic Utility of Pre- and Postoperative Circulating Tumor DNA Liquid Biopsies in Patients with Peritoneal Metastases

2020 ◽  
Vol 27 (9) ◽  
pp. 3259-3267
Author(s):  
Joel M. Baumgartner ◽  
Paul Riviere ◽  
Richard B. Lanman ◽  
Kaitlyn J. Kelly ◽  
Jula Veerapong ◽  
...  
Keyword(s):  
Circulating Tumor Dna ◽  
Peritoneal Metastases ◽  
Liquid Biopsies ◽  
Prognostic Utility ◽  
Tumor Dna

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 Toward liquid biopsies in cancer treatment: application of circulating tumor DNA

Apmis ◽  
2019 ◽  
Vol 127 (5) ◽  
pp. 329-336 ◽  
Author(s):  
Lise Barlebo Ahlborn ◽  
Olga Østrup
Keyword(s):  
Cancer Treatment ◽  
Circulating Tumor Dna ◽  
Liquid Biopsies ◽  
Tumor Dna ◽  
Treatment Application

scholarly journals Analysis of mutational and proteomic heterogeneity of gastric cancer suggests an effective pipeline to monitor post-treatment tumor burden using circulating tumor DNA

PLoS ONE ◽  
2020 ◽  
Vol 15 (10) ◽  
pp. e0239966
Author(s):  
Noriyuki Sasaki ◽  
Takeshi Iwaya ◽  
Takehiro Chiba ◽  
Masashi Fujita ◽  
Zhenlin Ju ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Circulating Tumor Dna ◽  
Tumor Burden ◽  
Post Treatment ◽  
Tumor Dna
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