Review of the clinical applications and technological advances of circulating tumor DNA in cancer monitoring

Chang, Yi; Tolani, Bhairavi; Nie, Xin; Zhi, Xiao; Hu, Mu; He, Biao

doi:10.2147/tcrm.s141991

Cited by 61 publications

(43 citation statements)

References 104 publications

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“…The growing interest to identify non-invasive alternatives to standard tissue biopsies has generated enormous attention for liquid biopsies over the last decade. Initial advances in cfDNA technology have paved the way for the development of clinically applicable cf-NA-based biomarkers [25][26][27] . cfDNA offers potential advantages compared to invasive tissue biopsies; however, cfDNA analyses largely rely on mutations, polymorphisms, or structural variations, compromising its use in disease and physiological scenarios not associated with genetic differences.…”

Section: Discussionmentioning

confidence: 99%

Non-invasive characterization of human bone marrow stimulation and reconstitution by cell-free messenger RNA sequencing

Ibarra¹,

Zhuang²,

Zhao³

et al. 2020

Nat Commun

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Circulating cell-free mRNA (cf-mRNA) holds great promise as a non-invasive diagnostic biomarker. However, cf-mRNA composition and its potential clinical applications remain largely unexplored. Here we show, using Next Generation Sequencing-based profiling, that cf-mRNA is enriched in transcripts derived from the bone marrow compared to circulating cells. Further, longitudinal studies involving bone marrow ablation followed by hematopoietic stem cell transplantation in multiple myeloma and acute myeloid leukemia patients indicate that cf-mRNA levels reflect the transcriptional activity of bone marrow-resident hematopoietic lineages during bone marrow reconstitution. Mechanistically, stimulation of specific bone marrow cell populations in vivo using growth factor pharmacotherapy show that cf-mRNA reflects dynamic functional changes over time associated with cellular activity. Our results shed light on the biology of the circulating transcriptome and highlight the potential utility of cf-mRNA to non-invasively monitor bone marrow involved pathologies.

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Section: Discussionmentioning

confidence: 99%

Non-invasive characterization of human bone marrow stimulation and reconstitution by cell-free messenger RNA sequencing

Ibarra¹,

Zhuang²,

Zhao³

et al. 2020

Nat Commun

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“…Furthermore, cfDNAs contain information on the mutations that affect treatment, facilitate individualized therapeutic examining, and non-invasive follow-up that may enable better cancer management [210]. However, the extraction and amplification of cfDNA can be demanding due to high DNA fragmentation and low concentration in the bloodstream [211].…”

Section: Circulating Free Dnamentioning

confidence: 99%

Tumor microenvironment complexity and therapeutic implications at a glance

et al. 2020

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The dynamic interactions of cancer cells with their microenvironment consisting of stromal cells (cellular part) and extracellular matrix (ECM) components (non-cellular) is essential to stimulate the heterogeneity of cancer cell, clonal evolution and to increase the multidrug resistance ending in cancer cell progression and metastasis. The reciprocal cell-cell/ECM interaction and tumor cell hijacking of non-malignant cells force stromal cells to lose their function and acquire new phenotypes that promote development and invasion of tumor cells. Understanding the underlying cellular and molecular mechanisms governing these interactions can be used as a novel strategy to indirectly disrupt cancer cell interplay and contribute to the development of efficient and safe therapeutic strategies to fight cancer. Furthermore, the tumor-derived circulating materials can also be used as cancer diagnostic tools to precisely predict and monitor the outcome of therapy. This review evaluates such potentials in various advanced cancer models, with a focus on 3D systems as well as lab-on-chip devices.

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“…The source of nonmutated genomic DNA is for the most part circulating lymphocytes and its release can be triggered during blood collection and plasma processing procedures (31,32). In general, protocols to process plasma recommend a first centrifugation of blood at low speed to enable the separation of plasma from blood cells, followed by a second high-speed centrifugation to minimize the contamination of plasma with nucleic acids from cellular debris (33,34). However, performing the second high-speed centrifugation is not always suitable in the clinical setting due to the lack of ultra-high-speed centrifuges in hospitals and also to the increased burden that it represents for clinical research associates and nurses.…”

Section: Impact Of Plasma Processing On Cfdna Levelsmentioning

confidence: 99%

A Study of Pre-Analytical Variables and Optimization of Extraction Method for Circulating Tumor DNA Measurements by Digital Droplet PCR

Cavallone

Aldamry

Lafleur

et al. 2019

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Circulating free DNA (cfDNA) is an exciting novel method to diagnose, monitor, and predict resistance and response to cancer therapies, with the potential to radically alter the management of cancer patients. To fulfill its potential, greater knowledge about preanalytical variables is required to optimize and standardize the collection process, and maximize the yield and utility of the small quantities of cfDNA extracted. Methods: To this end, we have compared the cfDNA extraction efficiency of three different protocols, including a protocol developed in house (Jewish General Hospital). We evaluated the impact on cfDNA levels of preanalytical variables including speed and timing of the second centrifugation and the use of k-EDTA and CTAD blood collection tubes. Finally, we analyzed the impact on fractional abundance of targeted pre-amplification and whole genome amplification on tumor and circulating tumor DNA (ctDNA) from patients with breast cancer. Results: Making use of a novel protocol for cfDNA extraction we increased cfDNA quantities, up to double that of commercial kits. We found that a second centrifugation at 3,000 g on frozen plasma is as efficient as a high-speed (16,000 g) centrifugation on fresh plasma and does not affect cfDNA levels. Conclusions: These results allow for the implementation of protocols more suitable to the clinical setting. Finally, we found that, unlike targeted gene amplification, whole genome amplification resulted in altered fractional abundance of selected ctDNA variants. Impact: Our study of the preanalytical variables affecting cfDNA recovery and testing will significantly enhance the quality and application of ctDNA testing in clinical oncology.

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Review of the clinical applications and technological advances of circulating tumor DNA in cancer monitoring

Cited by 61 publications

References 104 publications

Non-invasive characterization of human bone marrow stimulation and reconstitution by cell-free messenger RNA sequencing

Non-invasive characterization of human bone marrow stimulation and reconstitution by cell-free messenger RNA sequencing

Tumor microenvironment complexity and therapeutic implications at a glance

A Study of Pre-Analytical Variables and Optimization of Extraction Method for Circulating Tumor DNA Measurements by Digital Droplet PCR

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