Deep Sequencing of Cell-Free Peripheral Blood DNA as a Reliable Method for Confirming the Diagnosis of Myelodysplastic Syndrome

Albitar, Ferras; Ma, Wanhong; Diep, Kevin; Dios, de; Agersborg, Sally; Thangavelu, Maya; Brodie, Steve; Albitar, Mäher

doi:10.1089/gtmb.2015.0278

Cited by 12 publications

(12 citation statements)

References 22 publications

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“…In five cfDNA samples, some abnormalities were detected by NGS that were not detected by Sanger sequencing in DNA from cells. These results suggest that NGS analysis of cfDNA is a reliable approach for the detection of molecular abnormalities in MDS patients …”

Section: Myeloid Malignanciesmentioning

confidence: 83%

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Cell‐free DNA — Minimally invasive marker of hematological malignancies

Kubaczková

Vrábel

Sedlaříková

et al. 2017

European J of Haematology

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Although tumor cells are the most reliable source of tumor DNA, biopsy of the tumor is an invasive procedure that should be avoided in some cases. The main limitation of any biopsy is sampling of one tumor site, which may not represent all malignant clones due to the heterogeneity of the tumor. These clones respond to treatment differently and thus directly influence survival of the patient. Circulating cell-free DNA (cfDNA) is released from multiple tumor sites, reflects overall heterogeneity of the tumor, and correlates with its progression. Detection of tumor-specific genetic and epigenetic aberrations in cfDNA could have a direct impact on molecular diagnosis, prognosis, follow-up of disease, monitoring of minimal residual disease, and response to treatment. While most cfDNA data are still experimental, they are very promising. This review focuses on cfDNA in hematological malignancies. K E Y W O R D Sacute lymphoblastic leukemia, acute myeloid leukemia, multiple myeloma, myelodysplastic syndromes | INTRODUCTION AND HISTORYIn recent years, significant advances in diagnosis and treatment of cancer have been made. Nevertheless, invasive and painful procedures, such as tissue or bone marrow (BM) biopsy, are gold standard for disease diagnosis and monitoring. At the same time, they should be avoided in some cases-if BM is fibrotic or tumor tissue is not easily accessible.1 As a single tumor site is sampled during BM biopsy, it may not contain all malignant clones. 2,3 As these clones react to treatment differently, they directly influence survival of patients; thus, easily accessible markers that would mirror the entire heterogeneity of the tumor are sought after. Such putative markers are present in peripheral blood (PB), for example, circulating tumor cells (CTC) or circulating nucleic acids. 3,4 Biopsies of PB-the so-called liquid biopsies-are at the center of attention of researchers as well as clinicians and represent a newer and more comprehensive approach to obtain tumor information. Analysis of circulating molecules (microRNA, cell-free DNA, and others) as well as CTC might describe the tumor in more detail.Cell-free DNA (cfDNA) is one of these possibilities.CfDNA is formed by DNA fragments. These fragments are gathered from all tumor sites into circulation; thus, they mirror the complexity and heterogeneity of the entire tumor. 3 CfDNA may serve as an excellent diagnostic marker as it reflects the disease in more detail than existing biomarkers. Moreover, because of easy access, cfDNA sampling is suitable for repeated analyses. 4 As it correlates with disease progression, it could serve as a prognostic marker as well. 5,6The first reference of cfDNA dates back to 1948. In that year, CfDNA may shortly become such a marker. | CHARACTERISTICS OF CFDNAMolecules of cfDNA are extracellular fragments of short doublestranded DNA found in PB and other body fluids, for example, in urine, saliva, breast milk, and synovial fluid. 16,17 Generally, cfDNA is found in very low concentrations in PB of HD (10-100...

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Section: Myeloid Malignanciesmentioning

confidence: 83%

“…Mutations detected in gDNA were also detected in cfDNA, but in some cases, mutations in plasma cfDNA were not detected in gDNA. Based on these findings, they suggested that plasma cfDNA is more reliable than cellular gDNA in detecting mutations using HS sequencing …”

Section: Lymphoid Malignanciesmentioning

confidence: 99%

Cell‐free DNA — Minimally invasive marker of hematological malignancies

Kubaczková

Vrábel

Sedlaříková

et al. 2017

European J of Haematology

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“…Moreover, serial ctDNA analysis in CLL can allow monitoring of clonal dynamics and identify genomic changes associated with Richter's syndrome . ctDNA analysis is also a powerful tool in patients with myeloid malignancies, particularly myelodysplastic syndromes , and in those with plasma cell disorders, such as multiple myeloma , as ctDNA analysis can detect underlying genomic changes in the bone marrow and be used as a monitoring strategy to limit invasive bone marrow biopsies . The potential of these approaches is now coming to the forefront of research, with clinical applications likely to expand across the breadth of haematological malignancies.…”

Section: Cfdna Profiling In Haematological Malignanciesmentioning

confidence: 99%

The value of cell‐free DNA for molecular pathology

Stewart

Kothari

Moulière

et al. 2018

The Journal of Pathology

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Over the past decade, advances in molecular biology and genomics techniques have revolutionized the diagnosis and treatment of cancer. The technological advances in tissue profiling have also been applied to the study of cell-free nucleic acids, an area of increasing interest for molecular pathology. Cell-free nucleic acids are released from tumour cells into the surrounding body fluids and can be assayed non-invasively. The repertoire of genomic alterations in circulating tumour DNA (ctDNA) is reflective of both primary tumours and distant metastatic sites, and ctDNA can be sampled multiple times, thereby overcoming the limitations of the analysis of single biopsies. Furthermore, ctDNA can be sampled regularly to monitor response to treatment, to define the evolution of the tumour genome, and to assess the acquisition of resistance and minimal residual disease. Recently, clinical ctDNA assays have been approved for guidance of therapy, which is an exciting first step in translating cell-free nucleic acid research tests into clinical use for oncology. In this review, we discuss the advantages of cell-free nucleic acids as analytes in different body fluids, including blood plasma, urine, and cerebrospinal fluid, and their clinical applications in solid tumours and haematological malignancies. We will also discuss practical considerations for clinical deployment, such as preanalytical factors and regulatory requirements. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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“…Mutation profiling in MDS is also of prognostic significance [ 73 - 76 ]. Because of the many recurrent mutations in MDS, next generation sequencing (NGS) strategies are generally required [ 70 - 77 ]. Recently, comprehensive myeloid marker panels have been established and are used in clinical practice (Table 5 ) [ 70 - 77 ].…”

Section: Mutation Profiles In Mds and Pre-mds: Current Standards And mentioning

confidence: 99%

“…Because of the many recurrent mutations in MDS, next generation sequencing (NGS) strategies are generally required [ 70 - 77 ]. Recently, comprehensive myeloid marker panels have been established and are used in clinical practice (Table 5 ) [ 70 - 77 ]. Some of these panels may be more specific for MDS and pre-MDS conditions whereas others may cover all myeloid neoplasms, including MDS.…”

Section: Mutation Profiles In Mds and Pre-mds: Current Standards And mentioning

confidence: 99%

Proposed minimal diagnostic criteria for myelodysplastic syndromes (MDS) and potential pre-MDS conditions

et al. 2017

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Myelodysplastic syndromes (MDS) comprise a heterogeneous group of myeloid neoplasms characterized by peripheral cytopenia, dysplasia, and a variable clinical course with about 30% risk to transform to secondary acute myeloid leukemia (AML). In the past 15 years, diagnostic evaluations, prognostication, and treatment of MDS have improved substantially. However, with the discovery of molecular markers and advent of novel targeted therapies, new challenges have emerged in the complex field of MDS. For example, MDS-related molecular lesions may be detectable in healthy individuals and increase in prevalence with age. Other patients exhibit persistent cytopenia of unknown etiology without dysplasia. Although these conditions are potential pre-phases of MDS they may also transform into other bone marrow neoplasms. Recently identified molecular, cytogenetic, and flow-based parameters may add in the delineation and prognostication of these conditions. However, no generally accepted integrated classification and no related criteria are as yet available. In an attempt to address this challenge, an international consensus group discussed these issues in a working conference in July 2016. The outcomes of this conference are summarized in the present article which includes criteria and a proposal for the classification of pre-MDS conditions as well as updated minimal diagnostic criteria of MDS. Moreover, we propose diagnostic standards to delineate between ´normal´, pre-MDS, and MDS. These standards and criteria should facilitate diagnostic and prognostic evaluations in clinical studies as well as in clinical practice.

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Deep Sequencing of Cell-Free Peripheral Blood DNA as a Reliable Method for Confirming the Diagnosis of Myelodysplastic Syndrome

Abstract: These data suggest that cf-DNA when analyzed using NGS is a reliable approach for detecting molecular abnormalities in MDS and should be used to determine if bone marrow aspiration and biopsy are necessary.

Cited by 12 publications

References 22 publications

Cell‐free DNA — Minimally invasive marker of hematological malignancies

Cell‐free DNA — Minimally invasive marker of hematological malignancies

The value of cell‐free DNA for molecular pathology

Proposed minimal diagnostic criteria for myelodysplastic syndromes (MDS) and potential pre-MDS conditions

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