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TP53 isoform junction reads based analysis in malignant and normal contexts
TP53 is one of the most frequently altered genes in cancer; it can be inactivated by a number of different mechanisms. NM_000546.6 (ENST00000269305.9) is by far the predominant TP53 isoform, however a few other alternative isoforms have been described to be expressed at much lower levels. To better...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390641/ https://www.ncbi.nlm.nih.gov/pubmed/34446762 http://dx.doi.org/10.1038/s41598-021-96700-1 |
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author | Vural, Suleyman Chang, Lun-Ching Yee, Laura M. Sonkin, Dmitriy |
author_facet | Vural, Suleyman Chang, Lun-Ching Yee, Laura M. Sonkin, Dmitriy |
author_sort | Vural, Suleyman |
collection | PubMed |
description | TP53 is one of the most frequently altered genes in cancer; it can be inactivated by a number of different mechanisms. NM_000546.6 (ENST00000269305.9) is by far the predominant TP53 isoform, however a few other alternative isoforms have been described to be expressed at much lower levels. To better understand patterns of TP53 alternative isoforms expression in cancer and normal samples we performed exon-exon junction reads based analysis of TP53 isoforms using RNA-seq data from The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), and Genotype-Tissue Expression (GTEx) project. TP53 C-terminal alternative isoforms have abolished or severely decreased tumor suppressor activity, and therefore, an increase in fraction of TP53 C-terminal alternative isoforms may be expected in tumors with wild type TP53. Despite our expectation that there would be increase of fraction of TP53 C-terminal alternative isoforms, we observed no substantial increase in fraction of TP53 C-terminal alternative isoforms in TCGA tumors and CCLE cancer cell lines with wild type TP53, likely indicating that TP53 C-terminal alternative isoforms expression cannot be reliably selected for during tumor progression. |
format | Online Article Text |
id | pubmed-8390641 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-83906412021-09-01 TP53 isoform junction reads based analysis in malignant and normal contexts Vural, Suleyman Chang, Lun-Ching Yee, Laura M. Sonkin, Dmitriy Sci Rep Article TP53 is one of the most frequently altered genes in cancer; it can be inactivated by a number of different mechanisms. NM_000546.6 (ENST00000269305.9) is by far the predominant TP53 isoform, however a few other alternative isoforms have been described to be expressed at much lower levels. To better understand patterns of TP53 alternative isoforms expression in cancer and normal samples we performed exon-exon junction reads based analysis of TP53 isoforms using RNA-seq data from The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), and Genotype-Tissue Expression (GTEx) project. TP53 C-terminal alternative isoforms have abolished or severely decreased tumor suppressor activity, and therefore, an increase in fraction of TP53 C-terminal alternative isoforms may be expected in tumors with wild type TP53. Despite our expectation that there would be increase of fraction of TP53 C-terminal alternative isoforms, we observed no substantial increase in fraction of TP53 C-terminal alternative isoforms in TCGA tumors and CCLE cancer cell lines with wild type TP53, likely indicating that TP53 C-terminal alternative isoforms expression cannot be reliably selected for during tumor progression. Nature Publishing Group UK 2021-08-26 /pmc/articles/PMC8390641/ /pubmed/34446762 http://dx.doi.org/10.1038/s41598-021-96700-1 Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2021 https://creativecommons.org/licenses/by/4.0/Open Access This 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/) . |
spellingShingle | Article Vural, Suleyman Chang, Lun-Ching Yee, Laura M. Sonkin, Dmitriy TP53 isoform junction reads based analysis in malignant and normal contexts |
title | TP53 isoform junction reads based analysis in malignant and normal contexts |
title_full | TP53 isoform junction reads based analysis in malignant and normal contexts |
title_fullStr | TP53 isoform junction reads based analysis in malignant and normal contexts |
title_full_unstemmed | TP53 isoform junction reads based analysis in malignant and normal contexts |
title_short | TP53 isoform junction reads based analysis in malignant and normal contexts |
title_sort | tp53 isoform junction reads based analysis in malignant and normal contexts |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390641/ https://www.ncbi.nlm.nih.gov/pubmed/34446762 http://dx.doi.org/10.1038/s41598-021-96700-1 |
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