A Simple RNA Target Capture NGS Strategy for Fusion Genes Assessment in the Diagnostics of Pediatric B-cell Acute Lymphoblastic Leukemia

Varování

Publikace nespadá pod Lékařskou fakultu, ale pod Středoevropský technologický institut. Oficiální stránka publikace je na webu muni.cz.

Autoři	GRIONI Andrea FAZIO G. RIGAMONTI S. BYSTRÝ Vojtěch DANIELE G. DOSTÁLOVÁ Zuzana QUADRI M. SAITTA C. SILVESTRI D. SONGIA S. STORLAZZI C.T. BIONDI A. DARZENTAS Nikos CAZZANIGA G.
Rok publikování	2019
Druh	Článek v odborném periodiku
Časopis / Zdroj	HEMASPHERE
Fakulta / Pracoviště MU	Středoevropský technologický institut
Citace
www	https://insights.ovid.com/crossref?an=02014419-201906000-00009
Doi	http://dx.doi.org/10.1097/HS9.0000000000000250
Klíčová slova	HIGH-RISK; EXPRESSION; IKZF1; CRLF2
Popis	Acute lymphoblastic leukemia (ALL) is the most frequent pediatric cancer. Fusion genes are hallmarks of ALL, and they are used as biomarkers for risk stratification as well as targets for precision medicine. Hence, clinical diagnostics pursues broad and comprehensive strategies for accurate discovery of fusion genes. Currently, the gold standard methodologies for fusion gene detection are fluorescence in situ hybridization and polymerase chain reaction; these, however, lack sensitivity for the identification of new fusion genes and breakpoints. In this study, we implemented a simple operating procedure (OP) for detecting fusion genes. The OP employs RNA CaptureSeq, a versatile and effortless next-generation sequencing assay, and an in-house as well as a purpose-built bioinformatics pipeline for the subsequent data analysis. The OP was evaluated on a cohort of 89 B-cell precursor ALL (BCP-ALL) pediatric samples annotated as negative for fusion genes by the standard techniques. The OP confirmed 51 samples as negative for fusion genes, and, more importantly, it identified known (KMT2A rearrangements) as well as new fusion events (JAK2 rearrangements) in the remaining 38 investigated samples, of which 16 fusion genes had prognostic significance. Herein, we describe the OP and its deployment into routine ALL diagnostics, which will allow substantial improvements in both patient risk stratification and precision medicine.