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PIK3CA exon9 mutations associate with reduced survival, and are highly concordant between matching primary tumors and metastases in endometrial cancer
Mutations of the phosphoinositide-3-kinase (PI3K) catalytic subunit alpha gene (PIK3CA) are frequent in endometrial cancer. We sequenced exon9 and exon20 of PIK3CA in 280 primary endometrial cancers to assess the relationship with clinicopathologic variables, patient survival and associations with P...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578954/ https://www.ncbi.nlm.nih.gov/pubmed/28860563 http://dx.doi.org/10.1038/s41598-017-10717-z |
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author | Mjos, Siv Werner, Henrica M. J. Birkeland, Even Holst, Frederik Berg, Anna Halle, Mari K. Tangen, Ingvild L. Kusonmano, Kanthida Mauland, Karen K. Oyan, Anne M. Kalland, Karl-Henning Lewis, Aurélia E. Mills, Gordon B. Krakstad, Camilla Trovik, Jone Salvesen, Helga B. Hoivik, Erling A. |
author_facet | Mjos, Siv Werner, Henrica M. J. Birkeland, Even Holst, Frederik Berg, Anna Halle, Mari K. Tangen, Ingvild L. Kusonmano, Kanthida Mauland, Karen K. Oyan, Anne M. Kalland, Karl-Henning Lewis, Aurélia E. Mills, Gordon B. Krakstad, Camilla Trovik, Jone Salvesen, Helga B. Hoivik, Erling A. |
author_sort | Mjos, Siv |
collection | PubMed |
description | Mutations of the phosphoinositide-3-kinase (PI3K) catalytic subunit alpha gene (PIK3CA) are frequent in endometrial cancer. We sequenced exon9 and exon20 of PIK3CA in 280 primary endometrial cancers to assess the relationship with clinicopathologic variables, patient survival and associations with PIK3CA mRNA and phospho-AKT1 by gene expression and protein data, respectively. While PIK3CA mutations generally had no impact on survival, and were not associated with clinicopathological variables, patients with exon9 charge-changing mutations, providing a positive charge at the substituted amino acid residue, were associated with poor survival (p = 0.018). Furthermore, we characterized PIK3CA mutations in the metastatic setting, including 32 patients with matched primary tumors and metastases, and found a high level of concordance (85.7%; 6 out of 7 patients), suggesting limited heterogeneity. PIK3CA mRNA levels were increased in metastases compared to the primary tumors (p = 0.031), independent of PIK3CA mutation status, which rather associated with reduced PIK3CA mRNA expression. PIK3CA mutated tumors expressed higher p-AKT/AKT protein levels, both within primary (p < 0.001) and metastatic lesion (p = 0.010). Our results support the notion that the PI3K signaling pathway might be activated, both dependent- and independently of PIK3CA mutations, an aspect that should be considered when designing PIK3 pathway targeting strategies in endometrial cancer. |
format | Online Article Text |
id | pubmed-5578954 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55789542017-09-06 PIK3CA exon9 mutations associate with reduced survival, and are highly concordant between matching primary tumors and metastases in endometrial cancer Mjos, Siv Werner, Henrica M. J. Birkeland, Even Holst, Frederik Berg, Anna Halle, Mari K. Tangen, Ingvild L. Kusonmano, Kanthida Mauland, Karen K. Oyan, Anne M. Kalland, Karl-Henning Lewis, Aurélia E. Mills, Gordon B. Krakstad, Camilla Trovik, Jone Salvesen, Helga B. Hoivik, Erling A. Sci Rep Article Mutations of the phosphoinositide-3-kinase (PI3K) catalytic subunit alpha gene (PIK3CA) are frequent in endometrial cancer. We sequenced exon9 and exon20 of PIK3CA in 280 primary endometrial cancers to assess the relationship with clinicopathologic variables, patient survival and associations with PIK3CA mRNA and phospho-AKT1 by gene expression and protein data, respectively. While PIK3CA mutations generally had no impact on survival, and were not associated with clinicopathological variables, patients with exon9 charge-changing mutations, providing a positive charge at the substituted amino acid residue, were associated with poor survival (p = 0.018). Furthermore, we characterized PIK3CA mutations in the metastatic setting, including 32 patients with matched primary tumors and metastases, and found a high level of concordance (85.7%; 6 out of 7 patients), suggesting limited heterogeneity. PIK3CA mRNA levels were increased in metastases compared to the primary tumors (p = 0.031), independent of PIK3CA mutation status, which rather associated with reduced PIK3CA mRNA expression. PIK3CA mutated tumors expressed higher p-AKT/AKT protein levels, both within primary (p < 0.001) and metastatic lesion (p = 0.010). Our results support the notion that the PI3K signaling pathway might be activated, both dependent- and independently of PIK3CA mutations, an aspect that should be considered when designing PIK3 pathway targeting strategies in endometrial cancer. Nature Publishing Group UK 2017-08-31 /pmc/articles/PMC5578954/ /pubmed/28860563 http://dx.doi.org/10.1038/s41598-017-10717-z Text en © The Author(s) 2017 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Mjos, Siv Werner, Henrica M. J. Birkeland, Even Holst, Frederik Berg, Anna Halle, Mari K. Tangen, Ingvild L. Kusonmano, Kanthida Mauland, Karen K. Oyan, Anne M. Kalland, Karl-Henning Lewis, Aurélia E. Mills, Gordon B. Krakstad, Camilla Trovik, Jone Salvesen, Helga B. Hoivik, Erling A. PIK3CA exon9 mutations associate with reduced survival, and are highly concordant between matching primary tumors and metastases in endometrial cancer |
title | PIK3CA exon9 mutations associate with reduced survival, and are highly concordant between matching primary tumors and metastases in endometrial cancer |
title_full | PIK3CA exon9 mutations associate with reduced survival, and are highly concordant between matching primary tumors and metastases in endometrial cancer |
title_fullStr | PIK3CA exon9 mutations associate with reduced survival, and are highly concordant between matching primary tumors and metastases in endometrial cancer |
title_full_unstemmed | PIK3CA exon9 mutations associate with reduced survival, and are highly concordant between matching primary tumors and metastases in endometrial cancer |
title_short | PIK3CA exon9 mutations associate with reduced survival, and are highly concordant between matching primary tumors and metastases in endometrial cancer |
title_sort | pik3ca exon9 mutations associate with reduced survival, and are highly concordant between matching primary tumors and metastases in endometrial cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578954/ https://www.ncbi.nlm.nih.gov/pubmed/28860563 http://dx.doi.org/10.1038/s41598-017-10717-z |
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