THE IMPORTANCE OF TARGETED NEXT-GENERATION SEQUENCING USAGE IN CYTOGENETICALLY NORMAL MYELOID MALIGNANCIES Targeted next-generation sequencing usage in cytogenetically normal myeloid malignancies

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Emine Atli
Hakan Gurkan
Engin Atli
Hakki Onur Kirkizlar
Sinem Yalcintepe
Selma Demir
Ufuk Demirci
Damla Eker
Cisem Mail
Rasime Kalkan
Ahmet Muzaffer Demir


Keywords: Hematologic malignancies, NGS, karyotype, FISH


Advanced diagnostic methods give an advantage for the identification of the abnormalities in myeloid malignancies. Various researchers have shown the potential importance of genetic tests both before the onset of the disease and during the remission. Large testing panels prevents false negative results in myeloid malignancies. But the important question is how the results of conventional cytogenetic and molecular cytogenetic techniques can be merged together with NGS technologies. In this paper, we drew an algorithm for evaluation of the myeloid malignancies. In order to evaluate genetic abnormalities, we performed cytogenetics, molecular cytogenetics and NGS testing in hematologic malignancies. In this study, we analyzed 100 patients who admitted to Medical Genetics Laboratory within different type of myeloid malignancies. We highlighted the possible diagnostic algorithm for cytogenetically normal cases. We applied NGS 141 gene panel for cytogenetically normal patients and we detected two or more pathogenic variations in 61 out of 100 patients (61%). The pathogenic variation detection rate of NGS varies in disease groups: AML were 85% and MDS were 23%. Here, we identified 24 novel variation out of total pathogenic variations in myeloid malignancies. A total 18 novel variation were identified in AML and 6 novel variation were identified in MDS. Despite of long turnaround time, conventional techniques are still golden standard for myeloid malignancies but sometimes cryptic gene fusions or complex abnormalities cannot be identified easily by conventional techniques. In these conditions, advanced technologies like NGS are highly recommended.


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