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Clinically relevant molecular subtypes and genomic alteration-independent differentiation in gynecologic carcinosarcoma

Carcinosarcoma (CS) of the uterus or ovary is a rare, aggressive and biphasic neoplasm composed of carcinoma and sarcoma elements. Previous genomic studies have identified the driver genes and genomic properties associated with CS. However, there is still no molecular subtyping scheme with clinical...

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Autores principales: Gotoh, Osamu, Sugiyama, Yuko, Takazawa, Yutaka, Kato, Kazuyoshi, Tanaka, Norio, Omatsu, Kohei, Takeshima, Nobuhiro, Nomura, Hidetaka, Hasegawa, Kosei, Fujiwara, Keiichi, Taki, Mana, Matsumura, Noriomi, Noda, Tetsuo, Mori, Seiichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823358/
https://www.ncbi.nlm.nih.gov/pubmed/31672974
http://dx.doi.org/10.1038/s41467-019-12985-x
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author Gotoh, Osamu
Sugiyama, Yuko
Takazawa, Yutaka
Kato, Kazuyoshi
Tanaka, Norio
Omatsu, Kohei
Takeshima, Nobuhiro
Nomura, Hidetaka
Hasegawa, Kosei
Fujiwara, Keiichi
Taki, Mana
Matsumura, Noriomi
Noda, Tetsuo
Mori, Seiichi
author_facet Gotoh, Osamu
Sugiyama, Yuko
Takazawa, Yutaka
Kato, Kazuyoshi
Tanaka, Norio
Omatsu, Kohei
Takeshima, Nobuhiro
Nomura, Hidetaka
Hasegawa, Kosei
Fujiwara, Keiichi
Taki, Mana
Matsumura, Noriomi
Noda, Tetsuo
Mori, Seiichi
author_sort Gotoh, Osamu
collection PubMed
description Carcinosarcoma (CS) of the uterus or ovary is a rare, aggressive and biphasic neoplasm composed of carcinoma and sarcoma elements. Previous genomic studies have identified the driver genes and genomic properties associated with CS. However, there is still no molecular subtyping scheme with clinical relevance for this disease. Here, we sequence 109 CS samples, focusing on 596 genes. We identify four molecular subtypes that resemble those observed in endometrial carcinoma: POLE-mutated, microsatellite instability, copy number high, and copy number low subtypes. These molecular subtypes are linked with DNA repair deficiencies, potential therapeutic strategies, and multiple clinicopathological features, including patient outcomes. Multi-regional comparative sequencing reveals genomic alteration-independent CS cell differentiation. Transcriptome and DNA methylome analyses confirm epithelial-mesenchymal transition as a mechanism of sarcoma differentiation. The current study thus provides therapeutic possibilities for CS as well as clues to understanding the molecular histogenic mechanism of its development.
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spelling pubmed-68233582019-11-04 Clinically relevant molecular subtypes and genomic alteration-independent differentiation in gynecologic carcinosarcoma Gotoh, Osamu Sugiyama, Yuko Takazawa, Yutaka Kato, Kazuyoshi Tanaka, Norio Omatsu, Kohei Takeshima, Nobuhiro Nomura, Hidetaka Hasegawa, Kosei Fujiwara, Keiichi Taki, Mana Matsumura, Noriomi Noda, Tetsuo Mori, Seiichi Nat Commun Article Carcinosarcoma (CS) of the uterus or ovary is a rare, aggressive and biphasic neoplasm composed of carcinoma and sarcoma elements. Previous genomic studies have identified the driver genes and genomic properties associated with CS. However, there is still no molecular subtyping scheme with clinical relevance for this disease. Here, we sequence 109 CS samples, focusing on 596 genes. We identify four molecular subtypes that resemble those observed in endometrial carcinoma: POLE-mutated, microsatellite instability, copy number high, and copy number low subtypes. These molecular subtypes are linked with DNA repair deficiencies, potential therapeutic strategies, and multiple clinicopathological features, including patient outcomes. Multi-regional comparative sequencing reveals genomic alteration-independent CS cell differentiation. Transcriptome and DNA methylome analyses confirm epithelial-mesenchymal transition as a mechanism of sarcoma differentiation. The current study thus provides therapeutic possibilities for CS as well as clues to understanding the molecular histogenic mechanism of its development. Nature Publishing Group UK 2019-10-31 /pmc/articles/PMC6823358/ /pubmed/31672974 http://dx.doi.org/10.1038/s41467-019-12985-x Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Gotoh, Osamu
Sugiyama, Yuko
Takazawa, Yutaka
Kato, Kazuyoshi
Tanaka, Norio
Omatsu, Kohei
Takeshima, Nobuhiro
Nomura, Hidetaka
Hasegawa, Kosei
Fujiwara, Keiichi
Taki, Mana
Matsumura, Noriomi
Noda, Tetsuo
Mori, Seiichi
Clinically relevant molecular subtypes and genomic alteration-independent differentiation in gynecologic carcinosarcoma
title Clinically relevant molecular subtypes and genomic alteration-independent differentiation in gynecologic carcinosarcoma
title_full Clinically relevant molecular subtypes and genomic alteration-independent differentiation in gynecologic carcinosarcoma
title_fullStr Clinically relevant molecular subtypes and genomic alteration-independent differentiation in gynecologic carcinosarcoma
title_full_unstemmed Clinically relevant molecular subtypes and genomic alteration-independent differentiation in gynecologic carcinosarcoma
title_short Clinically relevant molecular subtypes and genomic alteration-independent differentiation in gynecologic carcinosarcoma
title_sort clinically relevant molecular subtypes and genomic alteration-independent differentiation in gynecologic carcinosarcoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823358/
https://www.ncbi.nlm.nih.gov/pubmed/31672974
http://dx.doi.org/10.1038/s41467-019-12985-x
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