TP53 isoform junction reads based analysis in malignant and normal contexts

Abstract 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. T...

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Autores principales: Suleyman Vural, Lun-Ching Chang, Laura M. Yee, Dmitriy Sonkin
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/8e296f6de39e4f9788c5d915b7962f4c
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spelling oai:doaj.org-article:8e296f6de39e4f9788c5d915b7962f4c2021-12-02T16:34:58ZTP53 isoform junction reads based analysis in malignant and normal contexts10.1038/s41598-021-96700-12045-2322https://doaj.org/article/8e296f6de39e4f9788c5d915b7962f4c2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96700-1https://doaj.org/toc/2045-2322Abstract 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.Suleyman VuralLun-Ching ChangLaura M. YeeDmitriy SonkinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-7 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Suleyman Vural
Lun-Ching Chang
Laura M. Yee
Dmitriy Sonkin
TP53 isoform junction reads based analysis in malignant and normal contexts
description Abstract 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 article
author Suleyman Vural
Lun-Ching Chang
Laura M. Yee
Dmitriy Sonkin
author_facet Suleyman Vural
Lun-Ching Chang
Laura M. Yee
Dmitriy Sonkin
author_sort Suleyman Vural
title 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_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_sort tp53 isoform junction reads based analysis in malignant and normal contexts
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/8e296f6de39e4f9788c5d915b7962f4c
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AT lunchingchang tp53isoformjunctionreadsbasedanalysisinmalignantandnormalcontexts
AT lauramyee tp53isoformjunctionreadsbasedanalysisinmalignantandnormalcontexts
AT dmitriysonkin tp53isoformjunctionreadsbasedanalysisinmalignantandnormalcontexts
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