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Whole-Genome DNA Methylation Profiling Identifies Epigenetic Signatures of Uterine Carcinosarcoma()()
Uterine carcinosarcoma (UCS) is a form of endometrial cancer simultaneously exhibiting carcinomatous and sarcomatous elements, but the underlying molecular and epigenetic basis of this disease is poorly understood. We generated complete DNA methylomes for both the carcinomatous and the sarcomatous c...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5237802/ https://www.ncbi.nlm.nih.gov/pubmed/28088687 http://dx.doi.org/10.1016/j.neo.2016.12.009 |
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author | Li, Jing Xing, Xiaoyun Li, Daofeng Zhang, Bo Mutch, David G. Hagemann, Ian S. Wang, Ting |
author_facet | Li, Jing Xing, Xiaoyun Li, Daofeng Zhang, Bo Mutch, David G. Hagemann, Ian S. Wang, Ting |
author_sort | Li, Jing |
collection | PubMed |
description | Uterine carcinosarcoma (UCS) is a form of endometrial cancer simultaneously exhibiting carcinomatous and sarcomatous elements, but the underlying molecular and epigenetic basis of this disease is poorly understood. We generated complete DNA methylomes for both the carcinomatous and the sarcomatous components of three UCS samples separated by laser capture microdissection and compared DNA methylomes of UCS with those of normal endometrium as well as methylomes derived from endometrioid carcinoma, serous endometrial carcinoma, and endometrial stromal sarcoma. We identified epigenetic lesions specific to carcinosarcoma and specific to its two components. Hallmarks of DNA methylation abnormalities in UCS included global hypomethylation, especially in repetitive elements, and hypermethylation of tumor suppressor gene promoters. Among these, aberrant DNA methylation of MIR200 genes is a key feature of UCS. The carcinoma component of UCS was characterized by hypermethylation of promoters of EMILIN1, NEFM, and CLEC14A, genes that are associated with tumor vascularization. In contrast, DNA methylation changes of PKP3, FAM83F, and TCP11 were more characteristic of the sarcoma components. Our findings highlight the epigenetic signatures that distinguish the two components of UCS, providing a valuable resource for investigation of this disease. |
format | Online Article Text |
id | pubmed-5237802 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-52378022017-01-23 Whole-Genome DNA Methylation Profiling Identifies Epigenetic Signatures of Uterine Carcinosarcoma()() Li, Jing Xing, Xiaoyun Li, Daofeng Zhang, Bo Mutch, David G. Hagemann, Ian S. Wang, Ting Neoplasia Original article Uterine carcinosarcoma (UCS) is a form of endometrial cancer simultaneously exhibiting carcinomatous and sarcomatous elements, but the underlying molecular and epigenetic basis of this disease is poorly understood. We generated complete DNA methylomes for both the carcinomatous and the sarcomatous components of three UCS samples separated by laser capture microdissection and compared DNA methylomes of UCS with those of normal endometrium as well as methylomes derived from endometrioid carcinoma, serous endometrial carcinoma, and endometrial stromal sarcoma. We identified epigenetic lesions specific to carcinosarcoma and specific to its two components. Hallmarks of DNA methylation abnormalities in UCS included global hypomethylation, especially in repetitive elements, and hypermethylation of tumor suppressor gene promoters. Among these, aberrant DNA methylation of MIR200 genes is a key feature of UCS. The carcinoma component of UCS was characterized by hypermethylation of promoters of EMILIN1, NEFM, and CLEC14A, genes that are associated with tumor vascularization. In contrast, DNA methylation changes of PKP3, FAM83F, and TCP11 were more characteristic of the sarcoma components. Our findings highlight the epigenetic signatures that distinguish the two components of UCS, providing a valuable resource for investigation of this disease. Neoplasia Press 2017-01-12 /pmc/articles/PMC5237802/ /pubmed/28088687 http://dx.doi.org/10.1016/j.neo.2016.12.009 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original article Li, Jing Xing, Xiaoyun Li, Daofeng Zhang, Bo Mutch, David G. Hagemann, Ian S. Wang, Ting Whole-Genome DNA Methylation Profiling Identifies Epigenetic Signatures of Uterine Carcinosarcoma()() |
title | Whole-Genome DNA Methylation Profiling Identifies Epigenetic Signatures of Uterine Carcinosarcoma()() |
title_full | Whole-Genome DNA Methylation Profiling Identifies Epigenetic Signatures of Uterine Carcinosarcoma()() |
title_fullStr | Whole-Genome DNA Methylation Profiling Identifies Epigenetic Signatures of Uterine Carcinosarcoma()() |
title_full_unstemmed | Whole-Genome DNA Methylation Profiling Identifies Epigenetic Signatures of Uterine Carcinosarcoma()() |
title_short | Whole-Genome DNA Methylation Profiling Identifies Epigenetic Signatures of Uterine Carcinosarcoma()() |
title_sort | whole-genome dna methylation profiling identifies epigenetic signatures of uterine carcinosarcoma()() |
topic | Original article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5237802/ https://www.ncbi.nlm.nih.gov/pubmed/28088687 http://dx.doi.org/10.1016/j.neo.2016.12.009 |
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