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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2021
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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) |
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RNA editing Pediatric cancer Genomics Immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
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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 |
work_keys_str_mv |
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