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Multiplexed automated digital quantification of fusion transcripts: comparative study with fluorescent in-situ hybridization (FISH) technique in acute leukemia patients

Overview of attention for article published in Diagnostic Pathology, September 2016
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Title
Multiplexed automated digital quantification of fusion transcripts: comparative study with fluorescent in-situ hybridization (FISH) technique in acute leukemia patients
Published in
Diagnostic Pathology, September 2016
DOI 10.1186/s13000-016-0541-z
Pubmed ID
Authors

Ariz Akhter, Muhammad Kashif Mughal, Ghaleb Elyamany, Gary Sinclair, Raja Zahratul Azma, Noraidah Masir, Salwati Shuib, Fariborz Rashid-Kolvear, Meer-Taher Shabani-Rad, Douglas Allan Stewart, Adnan Mansoor

Abstract

The World Health Organization (WHO) classification system defines recurrent chromosomal translocations as the sole diagnostic and prognostic criteria for acute leukemia (AL). These fusion transcripts are pivotal in the pathogenesis of AL. Clinical laboratories universally employ conventional karyotype/FISH to detect these chromosomal translocations, which is complex, labour intensive and lacks multiplexing capacity. Hence, it is imperative to explore and evaluate some newer automated, cost-efficient multiplexed technologies to accommodate the expanding genetic landscape in AL. "nCounter® Leukemia fusion gene expression assay" by NanoString was employed to detect various fusion transcripts in a large set samples (n = 94) utilizing RNA from formalin fixed paraffin embedded (FFPE) diagnostic bone marrow biopsy specimens. This series included AL patients with various recurrent translocations (n = 49), normal karyotype (n = 19), or complex karyotype (n = 21), as well as normal bone marrow samples (n = 5). Fusion gene expression data were compared with results obtained by conventional karyotype and FISH technology to determine sensitivity/specificity, as well as positive /negative predictive values. Junction probes for PML/RARA; RUNX1-RUNX1T1; BCR/ABL1 showed 100 % sensitivity/specificity. A high degree of correlation was noted for MLL/AF4 (85 sensitivity/100 specificity) and TCF3-PBX1 (75 % sensitivity/100 % specificity) probes. CBFB-MYH11 fusion probes showed moderate sensitivity (57 %) but high specificity (100 %). ETV6/RUNX1 displayed discordance between fusion transcript assay and FISH results as well as rare non-specific binding in AL samples with normal or complex cytogenetics. Our study presents preliminary data with high correlation between fusion transcript detection by a throughput automated multiplexed platform, compared to conventional karyotype/FISH technique for detection of chromosomal translocations in AL patients. Our preliminary observations, mandates further vast validation studies to explore automated molecular platforms in diagnostic pathology.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 26 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 5 19%
Other 3 12%
Student > Bachelor 2 8%
Student > Master 2 8%
Student > Doctoral Student 1 4%
Other 5 19%
Unknown 8 31%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 5 19%
Medicine and Dentistry 4 15%
Nursing and Health Professions 2 8%
Agricultural and Biological Sciences 2 8%
Unspecified 1 4%
Other 2 8%
Unknown 10 38%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 September 2016.
All research outputs
#18,471,305
of 22,888,307 outputs
Outputs from Diagnostic Pathology
#760
of 1,131 outputs
Outputs of similar age
#243,646
of 321,166 outputs
Outputs of similar age from Diagnostic Pathology
#9
of 13 outputs
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