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High expression of the p53 isoform γ is associated with reduced progression-free survival in uterine serous carcinoma
BACKGROUND: Uterine serous carcinoma (USC) is a rare but aggressive subtype of endometrial carcinoma. Large-scale comprehensive efforts have resulted in an improved molecular understanding of its pathogenesis, and the p53 pathway has been proposed as a key player and is potentially targetable. Here...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019524/ https://www.ncbi.nlm.nih.gov/pubmed/29940909 http://dx.doi.org/10.1186/s12885-018-4591-3 |
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author | Bischof, Katharina Knappskog, Stian Stefansson, Ingunn McCormack, Emmet Martin Trovik, Jone Werner, Henrica Maria Johanna Woie, Kathrine Gjertsen, Bjorn Tore Bjorge, Line |
author_facet | Bischof, Katharina Knappskog, Stian Stefansson, Ingunn McCormack, Emmet Martin Trovik, Jone Werner, Henrica Maria Johanna Woie, Kathrine Gjertsen, Bjorn Tore Bjorge, Line |
author_sort | Bischof, Katharina |
collection | PubMed |
description | BACKGROUND: Uterine serous carcinoma (USC) is a rare but aggressive subtype of endometrial carcinoma. Large-scale comprehensive efforts have resulted in an improved molecular understanding of its pathogenesis, and the p53 pathway has been proposed as a key player and is potentially targetable. Here we attempt to further portray the p53 pathway in USC by assessing p53 isoform expression. METHODS: We applied quantitative Real-Time PCRs (RT-qPCR) for expression analyses of total p53 mRNA as well as quantitative distinction of p53β, p53γ, and the total mRNA of amino-terminal truncated Δ40p53 and Δ133p53 in a retrospective cohort of 37 patients with USC. TP53 mutation status was assessed by targeted massive parallel sequencing. Findings were correlated with clinical data. RESULTS: The p53 isoform expression landscape in USCs was heterogeneous and dominated by total Δ133p53, while the distinct p53β and p53γ variants were found at much lower levels. The isoform expression profiles varied between samples, while their expression was independent of TP53 mutation status. We found high relative p53γ expression to be associated with reduced progression-free survival (PFS). CONCLUSIONS: This is the first indication that elevated p53γ expression is associated with reduced PFS in USC. This single-center study may offer some insight in the landscape of p53 isoform expression in USC, but further validation studies are crucial to understand the context-dependent and tissue-specific role of the p53 isoform network in gynecological cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4591-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6019524 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-60195242018-07-06 High expression of the p53 isoform γ is associated with reduced progression-free survival in uterine serous carcinoma Bischof, Katharina Knappskog, Stian Stefansson, Ingunn McCormack, Emmet Martin Trovik, Jone Werner, Henrica Maria Johanna Woie, Kathrine Gjertsen, Bjorn Tore Bjorge, Line BMC Cancer Research Article BACKGROUND: Uterine serous carcinoma (USC) is a rare but aggressive subtype of endometrial carcinoma. Large-scale comprehensive efforts have resulted in an improved molecular understanding of its pathogenesis, and the p53 pathway has been proposed as a key player and is potentially targetable. Here we attempt to further portray the p53 pathway in USC by assessing p53 isoform expression. METHODS: We applied quantitative Real-Time PCRs (RT-qPCR) for expression analyses of total p53 mRNA as well as quantitative distinction of p53β, p53γ, and the total mRNA of amino-terminal truncated Δ40p53 and Δ133p53 in a retrospective cohort of 37 patients with USC. TP53 mutation status was assessed by targeted massive parallel sequencing. Findings were correlated with clinical data. RESULTS: The p53 isoform expression landscape in USCs was heterogeneous and dominated by total Δ133p53, while the distinct p53β and p53γ variants were found at much lower levels. The isoform expression profiles varied between samples, while their expression was independent of TP53 mutation status. We found high relative p53γ expression to be associated with reduced progression-free survival (PFS). CONCLUSIONS: This is the first indication that elevated p53γ expression is associated with reduced PFS in USC. This single-center study may offer some insight in the landscape of p53 isoform expression in USC, but further validation studies are crucial to understand the context-dependent and tissue-specific role of the p53 isoform network in gynecological cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4591-3) contains supplementary material, which is available to authorized users. BioMed Central 2018-06-25 /pmc/articles/PMC6019524/ /pubmed/29940909 http://dx.doi.org/10.1186/s12885-018-4591-3 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Bischof, Katharina Knappskog, Stian Stefansson, Ingunn McCormack, Emmet Martin Trovik, Jone Werner, Henrica Maria Johanna Woie, Kathrine Gjertsen, Bjorn Tore Bjorge, Line High expression of the p53 isoform γ is associated with reduced progression-free survival in uterine serous carcinoma |
title | High expression of the p53 isoform γ is associated with reduced progression-free survival in uterine serous carcinoma |
title_full | High expression of the p53 isoform γ is associated with reduced progression-free survival in uterine serous carcinoma |
title_fullStr | High expression of the p53 isoform γ is associated with reduced progression-free survival in uterine serous carcinoma |
title_full_unstemmed | High expression of the p53 isoform γ is associated with reduced progression-free survival in uterine serous carcinoma |
title_short | High expression of the p53 isoform γ is associated with reduced progression-free survival in uterine serous carcinoma |
title_sort | high expression of the p53 isoform γ is associated with reduced progression-free survival in uterine serous carcinoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019524/ https://www.ncbi.nlm.nih.gov/pubmed/29940909 http://dx.doi.org/10.1186/s12885-018-4591-3 |
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