The diagnostic utility of targeted gene panel sequencing in discriminating etiologies of cytopenia.

08:00 EDT 26th July 2019 | BioPortfolio

Summary of "The diagnostic utility of targeted gene panel sequencing in discriminating etiologies of cytopenia."

The diagnostic utility of somatic mutations in the context of cytopenias is unclear: clonal hematopoiesis can be found in healthy individuals, patients with aplastic anemia (AA), clonal cytopenia of undetermined significance (CCUS) and myelodysplastic syndrome (MDS). We examined a cohort of 207 well-characterized cytopenic patients with a 640-gene next generation sequencing (NGS) panel and compared its diagnostic utility with a "virtual" 41 gene panel. TET2, SF3B1, ASXL1, and TP53 were the most commonly mutated genes (frequency>10%). Mutations in the 640 gene panel show high sensitivity (98.3%) but low specificity (47.6%) for diagnosis of MDS. Notably, mutations of splicing factors and genes in the RAS pathway are relatively specific to MDS. Furthermore, high variant allele frequency (VAF) predicts
when the VAF is set at 20% the positive predictive value (PPV) for MDS is 95.9% with a specificity of 95.3%. Presence of two or more somatic mutations with ≥10% VAF showed a PPV of 95.2%. While the "virtual" 41 gene panel showed a mild decrease in sensitivity (95.7% vs. 98.3%), 100% specificity was observed when either VAF was set at ≥20% (100% vs. 95.3%) or two or more somatic mutations had VAFs ≥10%. Our study shows targeted gene panel sequencing improves the diagnostic approach and accuracy for unexplained cytopenia with its high sensitivity and high PPV for MDS when applying VAF cutoffs; furthermore, a 41-gene panel was shown to have at least comparable performance characteristics to the large 640-gene panel. This article is protected by copyright. All rights reserved.


Journal Details

This article was published in the following journal.

Name: American journal of hematology
ISSN: 1096-8652


DeepDyve research library

PubMed Articles [19487 Associated PubMed Articles listed on BioPortfolio]

Clinical utility of a targeted next generation sequencing panel in severe and pediatric onset Mendelian diseases.

Next generation sequencing has provided great advancements in genetic diagnosis of Mendalian disorders. Simultaneous sequencing of many genes has become increasingly cheaper and faster. Recently, a nu...

Set up and validation of a targeted NGS approach for the diagnosis of lysosomal storage disorders.

Lysosomal storage disorders (LSD) are monogenic diseases, due to accumulation of specific undegraded substrates into lysosomes. LSD diagnosis could take several years, due to both poor knowledge of th...

Customized multigene panels in epilepsy: the best things come in small packages.

Over the past 10 years, the increasingly important role played by next-generation sequencing panels in the genetic diagnosis of epilepsy has led to a growing list of gene variants and a plethora of n...

Assessing the diagnostic yield of targeted next-generation sequencing for melanoma and gastrointestinal tumors.

A common rationale in molecular diagnostic laboratories is that implementation of next-generation sequencing (NGS) enables simultaneous multi-gene testing, allowing increased information benefit as co...

Whole exome and targeted gene sequencing to detect pathogenic recessive variants in early onset cerebellar ataxia.

Over 100 genetically distinct causal known loci for hereditary ataxia phenotype poses a challenge for diagnostic work-up for ataxia patients in a clinically relevant time and precision. In the present...

Clinical Trials [8666 Associated Clinical Trials listed on BioPortfolio]

Clinical Benefit of Using Molecular Profiling to Determine an Individualized Treatment Plan for Patients With High Grade Glioma

This is a 2 strata pilot trial within the Pacific Pediatric Neuro-Oncology Consortium (PNOC). The study will use a new treatment approach based on each patient's tumor gene expression, wh...

Integrative Sequencing In Germline and Hereditary Tumours

This study will investigate the utility of integrative sequencing of individuals and families at risk of hereditary cancer syndromes and will uncover novel contributors to tumourigenesis. ...

Lung Cancer Next Generation Sequencing Using the Oncomine Comprehensive Assay

Currently, publicly funded standard of care testing in Ontario for stage IV lung cancer patients uses individual gene tests to look for mutations in the EGFR and ALK genes. This testing br...

Evaluation of the Efficacy of the Sequencing Method by Gene-panel

In order to accelerate the identification of genes responsibles of PID, and to improve the diagnosis of PID, we would like to validate a rapid and targeted method of high-throughput sequen...

Pediatric Infectious Disease Precision Medicine Using Sequencing Evaluation of CSF

Prospective, multi-site, study to evaluate the diagnosis rate of DNA and RNA sequencing of cerebrospinal fluid for identification of pathogens directly in patients who have already had a s...

Medical and Biotech [MESH] Definitions

Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (IMMUNOTOXINS) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (see RADIOTHERAPY).

The audibility limit of discriminating sound intensity and pitch.

Techniques of nucleotide sequence analysis that increase the range, complexity, sensitivity, and accuracy of results by greatly increasing the scale of operations and thus the number of nucleotides, and the number of copies of each nucleotide sequenced. The sequencing may be done by analysis of the synthesis or ligation products, hybridization to preexisting sequences, etc.

A technique which uses synthetic oligonucleotides to direct the cell's inherent DNA repair system to correct a mutation at a specific site in an episome or chromosome.

Direct nucleotide sequencing of gene fragments from multiple housekeeping genes for the purpose of phylogenetic analysis, organism identification, and typing of species, strain, serovar, or other distinguishable phylogenetic level.

Quick Search

DeepDyve research library

Relevant Topics

Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...

DNA sequencing
DNA sequencing is the process of determining the precise order of nucleotides within a DNA molecule. During DNA sequencing, the bases of a small fragment of DNA are sequentially identified from signals emitted as each fragment is re-synthesized from a ...

Searches Linking to this Article