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PIK3CA mutation profiling in patients with breast cancer, using a highly sensitive detection system
PIK3CA mutations are common activating mutations associated with breast cancer (occurring in 20–30% of all cases) and are potent predictive markers for responses to PI3K inhibitors. Thus, it is important to develop sensitive methods to detect these mutations. We established a novel detection method...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113507/ https://www.ncbi.nlm.nih.gov/pubmed/29906308 http://dx.doi.org/10.1111/cas.13696 |
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author | Shimoi, Tatsunori Hamada, Akinobu Yamagishi, Marifu Hirai, Mitsuharu Yoshida, Masayuki Nishikawa, Tadaaki Sudo, Kazuki Shimomura, Akihiko Noguchi, Emi Yunokawa, Mayu Yonemori, Kan Shimizu, Chikako Kinoshita, Takayuki Fukuda, Takahiro Fujiwara, Yasuhiro Tamura, Kenji |
author_facet | Shimoi, Tatsunori Hamada, Akinobu Yamagishi, Marifu Hirai, Mitsuharu Yoshida, Masayuki Nishikawa, Tadaaki Sudo, Kazuki Shimomura, Akihiko Noguchi, Emi Yunokawa, Mayu Yonemori, Kan Shimizu, Chikako Kinoshita, Takayuki Fukuda, Takahiro Fujiwara, Yasuhiro Tamura, Kenji |
author_sort | Shimoi, Tatsunori |
collection | PubMed |
description | PIK3CA mutations are common activating mutations associated with breast cancer (occurring in 20–30% of all cases) and are potent predictive markers for responses to PI3K inhibitors. Thus, it is important to develop sensitive methods to detect these mutations. We established a novel detection method using a quenching probe (QP) system to identify PIK3CA mutations, using DNA from 309 breast cancer tissues. In a developmental cohort, we determined the optimal detection threshold of the QP system with human tumor DNA from 119 freshly frozen tumor samples. We found a 96% concordance rate with the QP system between DNA from 26 matching fresh‐frozen specimens and formalin‐fixed paraffin‐embedded (FFPE) specimens from the same patients, and known PIK3CA mutation status in the developmental cohort. In a validation cohort, we evaluated whether the threshold for judging mutations using the QP system with frozen specimen‐derived DNA was applicable with FFPE‐derived DNA. In the validation cohort, 30 DNA samples from 190 FFPE‐derived DNA samples with known PIK3CA mutation status were analyzed by direct sequencing (DS) and droplet digital PCR, in a blinded manner. The sensitivity and specificity of the droplet digital PCR results were 100% and 100% (QP system), and 60% and 100% (DS), respectively. We also analyzed the relationship between clinical outcomes and the PIK3CA mutational status of 309 breast cancer samples, including the developmental cohort and validation cohort samples. Multivariate analysis suggested that PIK3CA mutations, especially H1047R, were prognostic factors of relapse‐free survival. Our novel detection system could be more useful than DS for detecting clinical PIK3CA mutations. |
format | Online Article Text |
id | pubmed-6113507 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-61135072018-09-04 PIK3CA mutation profiling in patients with breast cancer, using a highly sensitive detection system Shimoi, Tatsunori Hamada, Akinobu Yamagishi, Marifu Hirai, Mitsuharu Yoshida, Masayuki Nishikawa, Tadaaki Sudo, Kazuki Shimomura, Akihiko Noguchi, Emi Yunokawa, Mayu Yonemori, Kan Shimizu, Chikako Kinoshita, Takayuki Fukuda, Takahiro Fujiwara, Yasuhiro Tamura, Kenji Cancer Sci Original Articles PIK3CA mutations are common activating mutations associated with breast cancer (occurring in 20–30% of all cases) and are potent predictive markers for responses to PI3K inhibitors. Thus, it is important to develop sensitive methods to detect these mutations. We established a novel detection method using a quenching probe (QP) system to identify PIK3CA mutations, using DNA from 309 breast cancer tissues. In a developmental cohort, we determined the optimal detection threshold of the QP system with human tumor DNA from 119 freshly frozen tumor samples. We found a 96% concordance rate with the QP system between DNA from 26 matching fresh‐frozen specimens and formalin‐fixed paraffin‐embedded (FFPE) specimens from the same patients, and known PIK3CA mutation status in the developmental cohort. In a validation cohort, we evaluated whether the threshold for judging mutations using the QP system with frozen specimen‐derived DNA was applicable with FFPE‐derived DNA. In the validation cohort, 30 DNA samples from 190 FFPE‐derived DNA samples with known PIK3CA mutation status were analyzed by direct sequencing (DS) and droplet digital PCR, in a blinded manner. The sensitivity and specificity of the droplet digital PCR results were 100% and 100% (QP system), and 60% and 100% (DS), respectively. We also analyzed the relationship between clinical outcomes and the PIK3CA mutational status of 309 breast cancer samples, including the developmental cohort and validation cohort samples. Multivariate analysis suggested that PIK3CA mutations, especially H1047R, were prognostic factors of relapse‐free survival. Our novel detection system could be more useful than DS for detecting clinical PIK3CA mutations. John Wiley and Sons Inc. 2018-07-28 2018-08 /pmc/articles/PMC6113507/ /pubmed/29906308 http://dx.doi.org/10.1111/cas.13696 Text en © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Shimoi, Tatsunori Hamada, Akinobu Yamagishi, Marifu Hirai, Mitsuharu Yoshida, Masayuki Nishikawa, Tadaaki Sudo, Kazuki Shimomura, Akihiko Noguchi, Emi Yunokawa, Mayu Yonemori, Kan Shimizu, Chikako Kinoshita, Takayuki Fukuda, Takahiro Fujiwara, Yasuhiro Tamura, Kenji PIK3CA mutation profiling in patients with breast cancer, using a highly sensitive detection system |
title |
PIK3CA mutation profiling in patients with breast cancer, using a highly sensitive detection system |
title_full |
PIK3CA mutation profiling in patients with breast cancer, using a highly sensitive detection system |
title_fullStr |
PIK3CA mutation profiling in patients with breast cancer, using a highly sensitive detection system |
title_full_unstemmed |
PIK3CA mutation profiling in patients with breast cancer, using a highly sensitive detection system |
title_short |
PIK3CA mutation profiling in patients with breast cancer, using a highly sensitive detection system |
title_sort | pik3ca mutation profiling in patients with breast cancer, using a highly sensitive detection system |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113507/ https://www.ncbi.nlm.nih.gov/pubmed/29906308 http://dx.doi.org/10.1111/cas.13696 |
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