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The landscape of coding RNA editing events in pediatric cancer

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...

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Autores principales: Wen, Ji, Rusch, Michael, Brady, Samuel W., Shao, Ying, Edmonson, Michael N., Shaw, Timothy I., Powers, Brent B., Tian, Liqing, Easton, John, Mullighan, Charles G., Gruber, Tanja, Ellison, David, Zhang, Jinghui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8597231/
https://www.ncbi.nlm.nih.gov/pubmed/34789196
http://dx.doi.org/10.1186/s12885-021-08956-5
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author Wen, Ji
Rusch, Michael
Brady, Samuel W.
Shao, Ying
Edmonson, Michael N.
Shaw, Timothy I.
Powers, Brent B.
Tian, Liqing
Easton, John
Mullighan, Charles G.
Gruber, Tanja
Ellison, David
Zhang, Jinghui
author_facet Wen, Ji
Rusch, Michael
Brady, Samuel W.
Shao, Ying
Edmonson, Michael N.
Shaw, Timothy I.
Powers, Brent B.
Tian, Liqing
Easton, John
Mullighan, Charles G.
Gruber, Tanja
Ellison, David
Zhang, Jinghui
author_sort Wen, Ji
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08956-5.
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spelling pubmed-85972312021-11-17 The landscape of coding RNA editing events in pediatric cancer Wen, Ji Rusch, Michael Brady, Samuel W. Shao, Ying Edmonson, Michael N. Shaw, Timothy I. Powers, Brent B. Tian, Liqing Easton, John Mullighan, Charles G. Gruber, Tanja Ellison, David Zhang, Jinghui BMC Cancer Research Article 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08956-5. BioMed Central 2021-11-17 /pmc/articles/PMC8597231/ /pubmed/34789196 http://dx.doi.org/10.1186/s12885-021-08956-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Wen, Ji
Rusch, Michael
Brady, Samuel W.
Shao, Ying
Edmonson, Michael N.
Shaw, Timothy I.
Powers, Brent B.
Tian, Liqing
Easton, John
Mullighan, Charles G.
Gruber, Tanja
Ellison, David
Zhang, Jinghui
The landscape of coding RNA editing events in pediatric cancer
title 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_short The landscape of coding RNA editing events in pediatric cancer
title_sort landscape of coding rna editing events in pediatric cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8597231/
https://www.ncbi.nlm.nih.gov/pubmed/34789196
http://dx.doi.org/10.1186/s12885-021-08956-5
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