Circulating cell-free nucleic acids: characteristics and applications

Pös, Ondrej; Bíró, Orsolya; Szemes, Tomáš; Nagy, Bálint

doi:10.1038/s41431-018-0132-4

Cited by 174 publications

(144 citation statements)

References 86 publications

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“…These circulating biomolecules in blood contain information linked to specific organ health. While most research effort has focused on circulating proteins and lipids, circulating cell-free nucleic acids (cf-NA) have recently emerged as a non-invasive tool for diagnosis and monitoring of health and disease 1 . For example, cell-free DNA (cfDNA), the most well-characterized cf-NA, has been utilized for prenatal diagnostics, transplant rejection prediction, and monitoring of cancer [2][3][4][5][6] .…”

mentioning

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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mentioning

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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“…For patients with tumors, the cfDNA fragments of tumor cells known as circulating tumor DNA(ctDNA) also were released to peripheral blood through apoptosis and necrosis of tumor cells [6,7] . Plasma ctDNA, which is a fragment about 150-200 bp [35] containing genetic information about the tumor, is of great significance to the diagnosis, treatment and monitoring of the disease.…”

Section: Discussionmentioning

confidence: 99%

RNF213 gene mutation of circulating tumor DNA in early diagnosis of NSCLC using targeted next-generation sequencing

Jiang¹,

Zhao²,

P³

et al. 2019

Preprint

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Introduction To distinguish early stage lung cancer from benign disease of the lung nodules, especially the lesions with ground-glass opacity (GGO) or ground-glass nodule (GGN), we assessed gene mutations of the ctDNA in peripheral blood by using targeted next-generation sequencing (NGS). Methods Single lung nodule patients without mediastinal lymph nodes or symptoms hardly diagnosed by chest CT and biomarker of lung cancer were enrolled. All patients received minimally invasive surgery but refused preoperative biopsy. Gene mutations of pre-operative blood samples were detected by targeted NGS. Mutations with statistical differences were screened in lung cancer and benign disease grouped by postoperative pathology. Gene expression was determined by immunohistochemistry. Highly expressed genes were selected as biomarkers to verify the mutations in peripheral blood. Results In training set, RNF213, KMT2D, CSMD3 and LRP1B genes mutated more frequently in early stage lung cancer (25cases) than benign nodules (18cases) (P<0.05). High expressions of RNF213 gene in lung cancers and low expressions in benign diseases were evaluated by immunohistochemistry. RNF213 gene mutated in 25% lung cancer samples in the validation set of 28 samples and showed high specificity (100%) and low sensibility (25.9%). In GGO and GGN patients, RNF213 mutated more frequently in early stage lung cancer compared to benign diseases (P<0.05). Conclusions RNF213 gene mutation was observed more frequently in early stage lung cancer, but rather than benign nodules. Mutation of RNF213 gene in peripheral blood may be a high specificity biomarker and valuable for early diagnosis of lung cancer.

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“…Unfortunately, methods available for scrutinizing the transcriptome from PBMCs are useful for research methods, but not ideal for broader applications at scale. Furthermore, methods using PBMCs fail to measure the cell-free transcripts, which have been associated with certain disease conditions, particularly for cancer patients and pregnant women (Ng et al, 2003;Pinzani et al, 2010;Pös et al, 2018;Souza et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

A clinically validated human capillary blood transcriptome test for global systems biology studies

Toma¹,

Pelle

Duval³

et al. 2020

Preprint

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Chronic diseases are the leading cause of morbidity and mortality globally. Yet, the majority of them have unknown etiologies, and genetic contribution is weak. In addition, many of the chronic diseases go through the cycles of relapse and remission, during which the genomic DNA does not change. This strongly suggests that human gene expression is the main driver of chronic disease onset and relapses. To identify the etiology of chronic diseases and develop more effective preventative measures, a comprehensive gene expression analysis of the human body is needed. Blood tissue is easy to access and contains a large number of expressed genes involved in many fundamental aspects of our physiology.We report here the development of a whole blood transcriptome clinical test that is high throughput, automated, inexpensive, and clinically validated. The test requires only 50 microliters of blood from a finger prick, enabling access by diverse populations that have been traditionally underrepresented in clinical research. The transcripts in the samples are preserved at the time of collection and can be stored and/or transported at ambient temperatures for up to 28 days. The sample preservative protects integrity, while also inactivating all pathogens (bacteria, fungi, and viruses), enabling safe transportation globally. Given its unique set of usability features and clinical performance, this test should be integrated into longitudinal, populationscale, systems biology studies.

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Circulating cell-free nucleic acids: characteristics and applications

Cited by 174 publications

References 86 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

RNF213 gene mutation of circulating tumor DNA in early diagnosis of NSCLC using targeted next-generation sequencing

A clinically validated human capillary blood transcriptome test for global systems biology studies

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