The RNA editing landscape in acute myeloid leukemia reveals associations with disease mutations and clinical outcome.


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Authors
Meduri, Eshwar 
Breeze, Charles 
Marando, Ludovica 
Richardson, Simon E 
Huntly, Brian JP 
Abstract

Several studies have documented aberrant RNA editing patterns across multiple tumors across large patient cohorts from The Cancer Genome Atlas (TCGA). However, studies on understanding the role of RNA editing in acute myeloid leukemia (AML) have been limited to smaller sample sizes. Using high throughput transcriptomic data from the TCGA, we demonstrated higher levels of editing as a predictor of poor outcome within the AML patient samples. Moreover, differential editing patterns were observed across individual AML genotypes. We also could demonstrate a negative association between the degree of editing and mRNA abundance for some transcripts, identifying the potential regulatory potential of RNA-editing in altering gene expression in AML. Further edQTL analysis suggests potential cis-regulatory mechanisms in RNA editing variation. Our work suggests a functional and regulatory role of RNA editing in the pathogenesis of AML and we extended our analysis to gain insight into the factors influencing altered levels of editing.

Description
Keywords
Cancer, Cancer systems biology, Transcriptomics
Journal Title
iScience
Conference Name
Journal ISSN
2589-0042
2589-0042
Volume Title
Publisher
Elsevier BV
Sponsorship
Cancer Research UK (C67279/A27957)
European Research Council (647685)
Cancer Research UK (25508)
Wellcome Trust (203151/Z/16/Z)
Wellcome Trust (079895/Z/06/Z)
Wellcome Trust (205254/Z/16/Z)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Medical Research Council (MR/M010392/1)
Wellcome Trust (100140/Z/12/Z)
Medical Research Council (MR/R009708/1)
National Institute for Health and Care Research (IS-BRC-1215-20014)
Medical Research Council (MC_PC_17230)