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Assessing mutant p53 in primary high-grade serous ovarian cancer using immunohistochemistry and massively parallel sequencing
The tumour suppressor p53 is mutated in cancer, including over 96% of high-grade serous ovarian cancer (HGSOC). Mutations cause loss of wild-type p53 function due to either gain of abnormal function of mutant p53 (mutp53), or absent to low mutp53. Massively parallel sequencing (MPS) enables increase...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4870633/ https://www.ncbi.nlm.nih.gov/pubmed/27189670 http://dx.doi.org/10.1038/srep26191 |
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author | Cole, Alexander J. Dwight, Trisha Gill, Anthony J. Dickson, Kristie-Ann Zhu, Ying Clarkson, Adele Gard, Gregory B. Maidens, Jayne Valmadre, Susan Clifton-Bligh, Roderick Marsh, Deborah J. |
author_facet | Cole, Alexander J. Dwight, Trisha Gill, Anthony J. Dickson, Kristie-Ann Zhu, Ying Clarkson, Adele Gard, Gregory B. Maidens, Jayne Valmadre, Susan Clifton-Bligh, Roderick Marsh, Deborah J. |
author_sort | Cole, Alexander J. |
collection | PubMed |
description | The tumour suppressor p53 is mutated in cancer, including over 96% of high-grade serous ovarian cancer (HGSOC). Mutations cause loss of wild-type p53 function due to either gain of abnormal function of mutant p53 (mutp53), or absent to low mutp53. Massively parallel sequencing (MPS) enables increased accuracy of detection of somatic variants in heterogeneous tumours. We used MPS and immunohistochemistry (IHC) to characterise HGSOCs for TP53 mutation and p53 expression. TP53 mutation was identified in 94% (68/72) of HGSOCs, 62% of which were missense. Missense mutations demonstrated high p53 by IHC, as did 35% (9/26) of non-missense mutations. Low p53 was seen by IHC in 62% of HGSOC associated with non-missense mutations. Most wild-type TP53 tumours (75%, 6/8) displayed intermediate p53 levels. The overall sensitivity of detecting a TP53 mutation based on classification as ‘Low’, ‘Intermediate’ or ‘High’ for p53 IHC was 99%, with a specificity of 75%. We suggest p53 IHC can be used as a surrogate marker of TP53 mutation in HGSOC; however, this will result in misclassification of a proportion of TP53 wild-type and mutant tumours. Therapeutic targeting of mutp53 will require knowledge of both TP53 mutations and mutp53 expression. |
format | Online Article Text |
id | pubmed-4870633 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48706332016-06-01 Assessing mutant p53 in primary high-grade serous ovarian cancer using immunohistochemistry and massively parallel sequencing Cole, Alexander J. Dwight, Trisha Gill, Anthony J. Dickson, Kristie-Ann Zhu, Ying Clarkson, Adele Gard, Gregory B. Maidens, Jayne Valmadre, Susan Clifton-Bligh, Roderick Marsh, Deborah J. Sci Rep Article The tumour suppressor p53 is mutated in cancer, including over 96% of high-grade serous ovarian cancer (HGSOC). Mutations cause loss of wild-type p53 function due to either gain of abnormal function of mutant p53 (mutp53), or absent to low mutp53. Massively parallel sequencing (MPS) enables increased accuracy of detection of somatic variants in heterogeneous tumours. We used MPS and immunohistochemistry (IHC) to characterise HGSOCs for TP53 mutation and p53 expression. TP53 mutation was identified in 94% (68/72) of HGSOCs, 62% of which were missense. Missense mutations demonstrated high p53 by IHC, as did 35% (9/26) of non-missense mutations. Low p53 was seen by IHC in 62% of HGSOC associated with non-missense mutations. Most wild-type TP53 tumours (75%, 6/8) displayed intermediate p53 levels. The overall sensitivity of detecting a TP53 mutation based on classification as ‘Low’, ‘Intermediate’ or ‘High’ for p53 IHC was 99%, with a specificity of 75%. We suggest p53 IHC can be used as a surrogate marker of TP53 mutation in HGSOC; however, this will result in misclassification of a proportion of TP53 wild-type and mutant tumours. Therapeutic targeting of mutp53 will require knowledge of both TP53 mutations and mutp53 expression. Nature Publishing Group 2016-05-18 /pmc/articles/PMC4870633/ /pubmed/27189670 http://dx.doi.org/10.1038/srep26191 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Cole, Alexander J. Dwight, Trisha Gill, Anthony J. Dickson, Kristie-Ann Zhu, Ying Clarkson, Adele Gard, Gregory B. Maidens, Jayne Valmadre, Susan Clifton-Bligh, Roderick Marsh, Deborah J. Assessing mutant p53 in primary high-grade serous ovarian cancer using immunohistochemistry and massively parallel sequencing |
title | Assessing mutant p53 in primary high-grade serous ovarian cancer using immunohistochemistry and massively parallel sequencing |
title_full | Assessing mutant p53 in primary high-grade serous ovarian cancer using immunohistochemistry and massively parallel sequencing |
title_fullStr | Assessing mutant p53 in primary high-grade serous ovarian cancer using immunohistochemistry and massively parallel sequencing |
title_full_unstemmed | Assessing mutant p53 in primary high-grade serous ovarian cancer using immunohistochemistry and massively parallel sequencing |
title_short | Assessing mutant p53 in primary high-grade serous ovarian cancer using immunohistochemistry and massively parallel sequencing |
title_sort | assessing mutant p53 in primary high-grade serous ovarian cancer using immunohistochemistry and massively parallel sequencing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4870633/ https://www.ncbi.nlm.nih.gov/pubmed/27189670 http://dx.doi.org/10.1038/srep26191 |
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