The landscape of coding RNA editing events in pediatric cancer

Abstract Background RNA editing leads to post-transcriptional variation in protein sequences and has important biological implications. We sought to elucidate the landscape of RNA editing events across pediatric cancers. Methods Using RNA-Seq data mapped by a pipeline designed to minimize mapping am...

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Autores principales: Ji Wen, Michael Rusch, Samuel W. Brady, Ying Shao, Michael N. Edmonson, Timothy I. Shaw, Brent B. Powers, Liqing Tian, John Easton, Charles G. Mullighan, Tanja Gruber, David Ellison, Jinghui Zhang
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Publicado: BMC 2021
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spelling oai:doaj.org-article:ee45d5cced7c45b7b5b564ed8ad29fba2021-11-21T12:30:23ZThe landscape of coding RNA editing events in pediatric cancer10.1186/s12885-021-08956-51471-2407https://doaj.org/article/ee45d5cced7c45b7b5b564ed8ad29fba2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12885-021-08956-5https://doaj.org/toc/1471-2407Abstract Background RNA editing leads to post-transcriptional variation in protein sequences and has important biological implications. We sought to elucidate the landscape of RNA editing events across pediatric cancers. Methods Using RNA-Seq data mapped by a pipeline designed to minimize mapping ambiguity, we investigated RNA editing in 711 pediatric cancers from the St. Jude/Washington University Pediatric Cancer Genome Project focusing on coding variants which can potentially increase protein sequence diversity. We combined de novo detection using paired tumor DNA-RNA data with analysis of known RNA editing sites. Results We identified 722 unique RNA editing sites in coding regions across pediatric cancers, 70% of which were nonsynonymous recoding variants. Nearly all editing sites represented the canonical A-to-I (n = 706) or C-to-U sites (n = 14). RNA editing was enriched in brain tumors compared to other cancers, including editing of glutamate receptors and ion channels involved in neurotransmitter signaling. RNA editing profiles of each pediatric cancer subtype resembled those of the corresponding normal tissue profiled by the Genotype-Tissue Expression (GTEx) project. Conclusions In this first comprehensive analysis of RNA editing events in pediatric cancer, we found that the RNA editing profile of each cancer subtype is similar to its normal tissue of origin. Tumor-specific RNA editing events were not identified indicating that successful immunotherapeutic targeting of RNA-edited peptides in pediatric cancer should rely on increased antigen presentation on tumor cells compared to normal but not on tumor-specific RNA editing per se.Ji WenMichael RuschSamuel W. BradyYing ShaoMichael N. EdmonsonTimothy I. ShawBrent B. PowersLiqing TianJohn EastonCharles G. MullighanTanja GruberDavid EllisonJinghui ZhangBMCarticleRNA editingPediatric cancerGenomicsImmunotherapyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBMC Cancer, Vol 21, Iss 1, Pp 1-14 (2021)
institution DOAJ
collection DOAJ
language EN
topic RNA editing
Pediatric cancer
Genomics
Immunotherapy
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle RNA editing
Pediatric cancer
Genomics
Immunotherapy
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Ji Wen
Michael Rusch
Samuel W. Brady
Ying Shao
Michael N. Edmonson
Timothy I. Shaw
Brent B. Powers
Liqing Tian
John Easton
Charles G. Mullighan
Tanja Gruber
David Ellison
Jinghui Zhang
The landscape of coding RNA editing events in pediatric cancer
description Abstract Background RNA editing leads to post-transcriptional variation in protein sequences and has important biological implications. We sought to elucidate the landscape of RNA editing events across pediatric cancers. Methods Using RNA-Seq data mapped by a pipeline designed to minimize mapping ambiguity, we investigated RNA editing in 711 pediatric cancers from the St. Jude/Washington University Pediatric Cancer Genome Project focusing on coding variants which can potentially increase protein sequence diversity. We combined de novo detection using paired tumor DNA-RNA data with analysis of known RNA editing sites. Results We identified 722 unique RNA editing sites in coding regions across pediatric cancers, 70% of which were nonsynonymous recoding variants. Nearly all editing sites represented the canonical A-to-I (n = 706) or C-to-U sites (n = 14). RNA editing was enriched in brain tumors compared to other cancers, including editing of glutamate receptors and ion channels involved in neurotransmitter signaling. RNA editing profiles of each pediatric cancer subtype resembled those of the corresponding normal tissue profiled by the Genotype-Tissue Expression (GTEx) project. Conclusions In this first comprehensive analysis of RNA editing events in pediatric cancer, we found that the RNA editing profile of each cancer subtype is similar to its normal tissue of origin. Tumor-specific RNA editing events were not identified indicating that successful immunotherapeutic targeting of RNA-edited peptides in pediatric cancer should rely on increased antigen presentation on tumor cells compared to normal but not on tumor-specific RNA editing per se.
format article
author Ji Wen
Michael Rusch
Samuel W. Brady
Ying Shao
Michael N. Edmonson
Timothy I. Shaw
Brent B. Powers
Liqing Tian
John Easton
Charles G. Mullighan
Tanja Gruber
David Ellison
Jinghui Zhang
author_facet Ji Wen
Michael Rusch
Samuel W. Brady
Ying Shao
Michael N. Edmonson
Timothy I. Shaw
Brent B. Powers
Liqing Tian
John Easton
Charles G. Mullighan
Tanja Gruber
David Ellison
Jinghui Zhang
author_sort Ji Wen
title The landscape of coding RNA editing events in pediatric cancer
title_short The landscape of coding RNA editing events in pediatric cancer
title_full The landscape of coding RNA editing events in pediatric cancer
title_fullStr The landscape of coding RNA editing events in pediatric cancer
title_full_unstemmed The landscape of coding RNA editing events in pediatric cancer
title_sort landscape of coding rna editing events in pediatric cancer
publisher BMC
publishDate 2021
url https://doaj.org/article/ee45d5cced7c45b7b5b564ed8ad29fba
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