Molecular disease monitoring using circulating tumor DNA in myelodysplastic syndromes

Yeh, Paul; Dickinson, Michael; Ftouni, Sarah; Hunter, Tane; Sinha, Devbarna; Wong, Stephen Q.; Agarwal, Rishu; Vedururu, Ravikiran; Doig, Kenneth D.; Fong, Chun Yew; Blombery, Piers; Westerman, David; Dawson, Mark A.; Dawson, Sarah‐Jane

doi:10.1182/blood-2016-09-740308

Cited by 54 publications

(48 citation statements)

References 27 publications

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“…In one study, a method for deconvoluting genome-wide bisulfite sequencing data was developed to produce ‘tissue methylation maps’ of cfDNA for pregnant women, cancer patients, transplantation patients, and healthy subjects, revealing percentage contributions by different tissues [135]. The clinical potential of this method has been substantiated by other studies [[182], [183], [184]], and has provided some insight regarding the composition, degradation and variation of cfDNA in urine [185]. However, some major drawbacks of bisulfite sequencing is the high level (84–96%) of degradation of input DNA during the bisulfite conversion process [186], high costs, and the recovery of limited information due to the low abundance of CpGs in the genome.…”

Section: Utility Of Cfdna In Clinical Oncologymentioning

confidence: 99%

The emerging role of cell-free DNA as a molecular marker for cancer management

Bronkhorst

Ungerer

Holdenrieder

2019

Biomolecular Detection and Quantification

432

375

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An increasing number of studies demonstrate the potential use of cell-free DNA (cfDNA) as a surrogate marker for multiple indications in cancer, including diagnosis, prognosis, and monitoring. However, harnessing the full potential of cfDNA requires (i) the optimization and standardization of preanalytical steps, (ii) refinement of current analysis strategies, and, perhaps most importantly, (iii) significant improvements in our understanding of its origin, physical properties, and dynamics in circulation. The latter knowledge is crucial for interpreting the associations between changes in the baseline characteristics of cfDNA and the clinical manifestations of cancer. In this review we explore recent advancements and highlight the current gaps in our knowledge concerning each point of contact between cfDNA analysis and the different stages of cancer management.

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Section: Utility Of Cfdna In Clinical Oncologymentioning

confidence: 99%

The emerging role of cell-free DNA as a molecular marker for cancer management

Bronkhorst

Ungerer

Holdenrieder

2019

Biomolecular Detection and Quantification

432

375

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“…These changes can include oncogenic driver mutations and thus increase blood cancer risk especially in older patients . As circulating cfDNA is mainly derived from hematopoetic cells, individuals with oncogenic driver mutation positive blood may either have increased risk of blood cancer or increased necrosis/apoptosis of premalignant hematopoetic cells . In a large WES datasets comprising 17 182 individuals in an analysis for risk factors for diabetes mellitus, such somatic mutations were present in 9.6% of age class 70–79 (n = 2299), 11.7% of age class 80–89 (n = 317), and 18.4% of age class ≥90 years (n = 103).…”

Section: Liquid Biopsy For Mutation Testing In Different Diagnostic Smentioning

confidence: 99%

A field guide for cancer diagnostics using cell‐free DNA: From principles to practice and clinical applications

Volckmar

Sültmann

Riediger

et al. 2017

Genes Chromosomes & Cancer

166

157

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Recently, many genome-wide profiling studies provided insights into the molecular make-up of major cancer types. The deeper understanding of these genetic alterations and their functional consequences led to the discovery of novel therapeutic opportunities improving clinical management of cancer patients. While tissue-based molecular patient stratification is the gold standard for precision medicine, it has certain limitations: Tissue biopsies are invasive sampling procedures carrying the risk of complications and may not represent the entire tumor due to underlying genetic heterogeneity. In this context, complementary characterization of genetic information in the blood of cancer patients can serve as minimal-invasive 'liquid biopsy'. Fragments of circulating cell-free DNA (cfDNA) are released from tissues of healthy individuals as well as cancer patients. The fraction of cfDNA that is released from primary tumors or metastases (i.e. circulating tumor DNA, ctDNA) represents genetic aberrations in cancer cells, which are a potential source for diagnostic, prognostic, and predictive biomarkers. Recent studies have demonstrated technical feasibility and clinical applications including detection of drug targets and resistance mutations as well as longitudinal monitoring of tumors under therapy. To this end, a variety of pre-analytical procedures for blood processing, isolation and quantification of cfDNA are being employed and several analytical methods and technologies ranging from PCR-based single locus assays to genome-wide approaches are available, which considerably differ in sensitivity, specificity, and throughput. However, broad implementation of ctDNA analysis in daily clinical practice requires a thorough understanding of theoretical, technical, and biological concepts and necessitates standardization and validation of pre-analytical and analytical procedures across different technologies. Here, we review the pertinent literature and discuss the advantages and limitations of available methodologies and their potential applications in molecular diagnostics.

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“…Low levels of these molecules can be found even in healthy individuals; however, levels of cfDNA were found to be considerably elevated in various pathological conditions . The use of cfDNA for MRD evaluation in various hematological malignancies was described several times as having promising results . Moreover, cheap, reliable, and sensitive method of detection of these molecules and MRD in general is one of the top priorities in the field.…”

Section: Introductionmentioning

confidence: 99%

“…9 The use of cfDNA for MRD evaluation in various hematological malignancies was described several times as having promising results. [11][12][13] Moreover, cheap, reliable, and sensitive method of detection of these molecules and MRD in general is one of the top priorities in the field. Unfortunately, most of the studies evaluating MRD using cfDNA lack not only sufficient number of patients, but also longer observation times to draw conclusions.…”

Section: Introductionmentioning

confidence: 99%

Dynamics of tumor‐specific cfDNA in response to therapy in multiple myeloma patients

Vrábel

Sedlaříková

Besse

et al. 2019

European J of Haematology

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Objectives Progress in multiple myeloma treatment allows patients to achieve deeper responses, for which the assessment of minimal residual disease (MRD) is critical. Typically, bone marrow samples are used for this purpose; however, this approach is site‐limited. Liquid biopsy represents a minimally invasive and more comprehensive technique that is not site‐limited, but equally challenging. Methods While majority of current data comes from short‐term studies, we present a long‐term study on blood‐based MRD monitoring using tumor‐specific cell‐free DNA detection by ASO‐qPCR. One hundred and twelve patients were enrolled into the study, but long‐term sampling and analysis were feasible only in 45 patients. Results We found a significant correlation of quantity of tumor‐specific cell‐free DNA levels with clinically meaningful events [induction therapy (P = .004); ASCT (P = .012)]. Moreover, length of cfDNA fragments is associated with better treatment response of patients. Conclusions These results support the concept of tumor‐specific cell‐free DNA as a prognostic marker.

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Molecular disease monitoring using circulating tumor DNA in myelodysplastic syndromes

Abstract: Key Points Circulating tumor DNA can monitor disease and predict treatment failure by tracking driver mutations and karyotypic abnormalities in MDS.

Cited by 54 publications

References 27 publications

The emerging role of cell-free DNA as a molecular marker for cancer management

The emerging role of cell-free DNA as a molecular marker for cancer management

A field guide for cancer diagnostics using cell‐free DNA: From principles to practice and clinical applications

Dynamics of tumor‐specific cfDNA in response to therapy in multiple myeloma patients

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