title: Diagnostic evaluation of RNA sequencing for the detection of genetic abnormalities associated with Ph-like acute lymphoblastic leukemia (ALL).
abstract: Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) is a molecular subtype of high-risk B-cell ALL characterized by formation of abnormal gene fusions involving tyrosine kinase (TK) and cytokine receptor genes and activation of TK signaling. Because of the diversity of associated genetic changes, the detection of Ph-like ALL cases currently requires multiple cytogenetic and molecular assays; thus, our goal was to develop a consolidated workflow for detecting genetic abnormalities in Ph-like ALL. We found that total and targeted RNA sequencing (RNAseq)-based approach allowed the detection of abnormal fusion transcripts (EBF1-PDGFRB, P2RY8-CRLF2, RCSD1-ABL1, and RCSD1-ABL2). The bioinformatics algorithm accurately detected the fusion transcripts without prior input about possible events. Additionally, we showed that RNAseq analysis enabled evaluation for disease-associated sequence variants in expressed transcripts. While total RNAseq can be a second tier approach allowing discovery of novel genetic alterations, the targeted RNAseq workflow offers a clinically applicable method for the detection of fusion transcripts.
authors.affiliation: a Department of Medicine, Section of Hematology/Oncology , The University of Chicago , Chicago , IL , USA.
authors.forename: Kai Lee
authors.initials: KL
authors.lastname: Yap
authors.affiliation: b Department of Pathology , The University of Chicago , Chicago , IL , USA.
authors.forename: Larissa V
authors.initials: LV
authors.lastname: Furtado
authors.affiliation: a Department of Medicine, Section of Hematology/Oncology , The University of Chicago , Chicago , IL , USA.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Kiyotani
authors.affiliation: a Department of Medicine, Section of Hematology/Oncology , The University of Chicago , Chicago , IL , USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Curran
authors.affiliation: a Department of Medicine, Section of Hematology/Oncology , The University of Chicago , Chicago , IL , USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Stock
authors.affiliation: c Department of Pediatrics, Section of Pediatric Hematology/Oncology , The University of Chicago , Chicago , IL , USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: McNeer
authors.affiliation: b Department of Pathology , The University of Chicago , Chicago , IL , USA.
authors.forename: Sabah
authors.initials: S
authors.lastname: Kadri
authors.affiliation: b Department of Pathology , The University of Chicago , Chicago , IL , USA.
authors.forename: Jeremy P
authors.initials: JP
authors.lastname: Segal
authors.affiliation: a Department of Medicine, Section of Hematology/Oncology , The University of Chicago , Chicago , IL , USA.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: a Department of Medicine, Section of Hematology/Oncology , The University of Chicago , Chicago , IL , USA.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Le Beau
authors.affiliation: b Department of Pathology , The University of Chicago , Chicago , IL , USA.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Gurbuxani
authors.affiliation: a Department of Medicine, Section of Hematology/Oncology , The University of Chicago , Chicago , IL , USA.
authors.forename: Gordana
authors.initials: G
authors.lastname: Raca
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D056905:Chromosome Breakpoints; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics*; D017423:Sequence Analysis, RNA; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: D016044:Fusion Proteins, bcr-abl
keywords: Ph-like ALL; RNAseq; expression; fusion transcripts; sequence variant