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Genomic, Epigenomic, and Transcriptomic Profiling towards Identifying Omics Features and Specific Biomarkers That Distinguish Uterine Leiomyosarcoma and Leiomyoma at Molecular Levels

Uterine leiomyosarcoma (LMS) is the worst malignancy among the gynecologic cancers. Uterine leiomyoma (LM), a benign tumor of myometrial origin, is the most common among women of childbearing age. Because of their similar symptoms, it is difficult to preoperatively distinguish the two conditions onl...

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Autores principales: Miyata, Tomoko, Sonoda, Kenzo, Tomikawa, Junko, Tayama, Chiharu, Okamura, Kohji, Maehara, Kayoko, Kobayashi, Hiroaki, Wake, Norio, Kato, Kiyoko, Hata, Kenichiro, Nakabayashi, Kazuhiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4707342/
https://www.ncbi.nlm.nih.gov/pubmed/27057136
http://dx.doi.org/10.1155/2015/412068
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author Miyata, Tomoko
Sonoda, Kenzo
Tomikawa, Junko
Tayama, Chiharu
Okamura, Kohji
Maehara, Kayoko
Kobayashi, Hiroaki
Wake, Norio
Kato, Kiyoko
Hata, Kenichiro
Nakabayashi, Kazuhiko
author_facet Miyata, Tomoko
Sonoda, Kenzo
Tomikawa, Junko
Tayama, Chiharu
Okamura, Kohji
Maehara, Kayoko
Kobayashi, Hiroaki
Wake, Norio
Kato, Kiyoko
Hata, Kenichiro
Nakabayashi, Kazuhiko
author_sort Miyata, Tomoko
collection PubMed
description Uterine leiomyosarcoma (LMS) is the worst malignancy among the gynecologic cancers. Uterine leiomyoma (LM), a benign tumor of myometrial origin, is the most common among women of childbearing age. Because of their similar symptoms, it is difficult to preoperatively distinguish the two conditions only by ultrasound and pelvic MRI. While histopathological diagnosis is currently the main approach used to distinguish them postoperatively, unusual histologic variants of LM tend to be misdiagnosed as LMS. Therefore, development of molecular diagnosis as an alternative or confirmatory means will help to diagnose LMS more accurately. We adopted omics-based technologies to identify genome-wide features to distinguish LMS from LM and revealed that copy number, gene expression, and DNA methylation profiles successfully distinguished these tumors. LMS was found to possess features typically observed in malignant solid tumors, such as extensive chromosomal abnormalities, overexpression of cell cycle-related genes, hypomethylation spreading through large genomic regions, and frequent hypermethylation at the polycomb group target genes and protocadherin genes. We also identified candidate expression and DNA methylation markers, which will facilitate establishing postoperative molecular diagnostic tests based on conventional quantitative assays. Our results demonstrate the feasibility of establishing such tests and the possibility of developing preoperative and noninvasive methods.
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spelling pubmed-47073422016-04-07 Genomic, Epigenomic, and Transcriptomic Profiling towards Identifying Omics Features and Specific Biomarkers That Distinguish Uterine Leiomyosarcoma and Leiomyoma at Molecular Levels Miyata, Tomoko Sonoda, Kenzo Tomikawa, Junko Tayama, Chiharu Okamura, Kohji Maehara, Kayoko Kobayashi, Hiroaki Wake, Norio Kato, Kiyoko Hata, Kenichiro Nakabayashi, Kazuhiko Sarcoma Research Article Uterine leiomyosarcoma (LMS) is the worst malignancy among the gynecologic cancers. Uterine leiomyoma (LM), a benign tumor of myometrial origin, is the most common among women of childbearing age. Because of their similar symptoms, it is difficult to preoperatively distinguish the two conditions only by ultrasound and pelvic MRI. While histopathological diagnosis is currently the main approach used to distinguish them postoperatively, unusual histologic variants of LM tend to be misdiagnosed as LMS. Therefore, development of molecular diagnosis as an alternative or confirmatory means will help to diagnose LMS more accurately. We adopted omics-based technologies to identify genome-wide features to distinguish LMS from LM and revealed that copy number, gene expression, and DNA methylation profiles successfully distinguished these tumors. LMS was found to possess features typically observed in malignant solid tumors, such as extensive chromosomal abnormalities, overexpression of cell cycle-related genes, hypomethylation spreading through large genomic regions, and frequent hypermethylation at the polycomb group target genes and protocadherin genes. We also identified candidate expression and DNA methylation markers, which will facilitate establishing postoperative molecular diagnostic tests based on conventional quantitative assays. Our results demonstrate the feasibility of establishing such tests and the possibility of developing preoperative and noninvasive methods. Hindawi Publishing Corporation 2015 2015-12-28 /pmc/articles/PMC4707342/ /pubmed/27057136 http://dx.doi.org/10.1155/2015/412068 Text en Copyright © 2015 Tomoko Miyata et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Miyata, Tomoko
Sonoda, Kenzo
Tomikawa, Junko
Tayama, Chiharu
Okamura, Kohji
Maehara, Kayoko
Kobayashi, Hiroaki
Wake, Norio
Kato, Kiyoko
Hata, Kenichiro
Nakabayashi, Kazuhiko
Genomic, Epigenomic, and Transcriptomic Profiling towards Identifying Omics Features and Specific Biomarkers That Distinguish Uterine Leiomyosarcoma and Leiomyoma at Molecular Levels
title Genomic, Epigenomic, and Transcriptomic Profiling towards Identifying Omics Features and Specific Biomarkers That Distinguish Uterine Leiomyosarcoma and Leiomyoma at Molecular Levels
title_full Genomic, Epigenomic, and Transcriptomic Profiling towards Identifying Omics Features and Specific Biomarkers That Distinguish Uterine Leiomyosarcoma and Leiomyoma at Molecular Levels
title_fullStr Genomic, Epigenomic, and Transcriptomic Profiling towards Identifying Omics Features and Specific Biomarkers That Distinguish Uterine Leiomyosarcoma and Leiomyoma at Molecular Levels
title_full_unstemmed Genomic, Epigenomic, and Transcriptomic Profiling towards Identifying Omics Features and Specific Biomarkers That Distinguish Uterine Leiomyosarcoma and Leiomyoma at Molecular Levels
title_short Genomic, Epigenomic, and Transcriptomic Profiling towards Identifying Omics Features and Specific Biomarkers That Distinguish Uterine Leiomyosarcoma and Leiomyoma at Molecular Levels
title_sort genomic, epigenomic, and transcriptomic profiling towards identifying omics features and specific biomarkers that distinguish uterine leiomyosarcoma and leiomyoma at molecular levels
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4707342/
https://www.ncbi.nlm.nih.gov/pubmed/27057136
http://dx.doi.org/10.1155/2015/412068
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