Integrated genomic characterization of endometrial carcinoma
We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low o...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2013
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3704730/ https://www.ncbi.nlm.nih.gov/pubmed/23636398 http://dx.doi.org/10.1038/nature12113 |
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author | Levine, Douglas A. |
author_facet | Levine, Douglas A. |
author_sort | Levine, Douglas A. |
collection | PubMed |
description | We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature12113) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-3704730 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-37047302013-11-02 Integrated genomic characterization of endometrial carcinoma Levine, Douglas A. Nature Article We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature12113) contains supplementary material, which is available to authorized users. Nature Publishing Group UK 2013-05-01 2013 /pmc/articles/PMC3704730/ /pubmed/23636398 http://dx.doi.org/10.1038/nature12113 Text en © The Author(s) 2013 This work is licensed under a Creative Commons Attribution-Non-Commercial-ShareAlike 3.0 Unported licence. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-sa/3.0/. |
spellingShingle | Article Levine, Douglas A. Integrated genomic characterization of endometrial carcinoma |
title | Integrated genomic characterization of endometrial carcinoma |
title_full | Integrated genomic characterization of endometrial carcinoma |
title_fullStr | Integrated genomic characterization of endometrial carcinoma |
title_full_unstemmed | Integrated genomic characterization of endometrial carcinoma |
title_short | Integrated genomic characterization of endometrial carcinoma |
title_sort | integrated genomic characterization of endometrial carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3704730/ https://www.ncbi.nlm.nih.gov/pubmed/23636398 http://dx.doi.org/10.1038/nature12113 |
work_keys_str_mv | AT levinedouglasa integratedgenomiccharacterizationofendometrialcarcinoma AT integratedgenomiccharacterizationofendometrialcarcinoma |