Molecular Basis of Tumor Heterogeneity in Endometrial Carcinosarcoma

Endometrial carcinosarcoma (ECS) represents one of the most extreme examples of tumor heterogeneity among human cancers. ECS is a clinically aggressive, high-grade, metaplastic carcinoma. At the morphological level, intratumor heterogeneity in ECS is due to an admixture of epithelial (carcinoma) and...

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Autores: Leskela, Susanna, Pérez Mies, Belén, Rosa Rosa, Juan Manuel, Cristobal, Eva, Biscuola, Michele, Palacios Berraquero, María L., Ong, SuFey, Matias-Guiu, Xavier, 1958-, Palacios, José
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/171362
Acceso en línea:https://hdl.handle.net/2445/171362
Access Level:acceso abierto
Palabra clave:Càncer d'endometri
Expressió gènica
Endometrial cancer
Gene expression
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spelling Molecular Basis of Tumor Heterogeneity in Endometrial CarcinosarcomaLeskela, SusannaPérez Mies, BelénRosa Rosa, Juan ManuelCristobal, EvaBiscuola, MichelePalacios Berraquero, María L.Ong, SuFeyMatias-Guiu, Xavier, 1958-Palacios, JoséCàncer d'endometriExpressió gènicaEndometrial cancerGene expressionEndometrial carcinosarcoma (ECS) represents one of the most extreme examples of tumor heterogeneity among human cancers. ECS is a clinically aggressive, high-grade, metaplastic carcinoma. At the morphological level, intratumor heterogeneity in ECS is due to an admixture of epithelial (carcinoma) and mesenchymal (sarcoma) components that can include heterologous tissues, such as skeletal muscle, cartilage, or bone. Most ECSs belong to the copy-number high serous-like molecular subtype of endometrial carcinoma, characterized by the TP53 mutation and the frequently accompanied by a large number of gene copy-number alterations, including the amplification of important oncogenes, such as CCNE1 and c-MYC. However, a proportion of cases (20%) probably represent the progression of tumors initially belonging to the copy-number low endometrioid-like molecular subtype (characterized by mutations in genes such as PTEN, PI3KCA, or ARID1A), after the acquisition of the TP53 mutations. Only a few ECS belong to the microsatellite-unstable hypermutated molecular type and the POLE-mutated, ultramutated molecular type. A common characteristic of all ECSs is the modulation of genes involved in the epithelial to mesenchymal process. Thus, the acquisition of a mesenchymal phenotype is associated with a switch from E- to N-cadherin, the up-regulation of transcriptional repressors of E-cadherin, such as Snail Family Transcriptional Repressor 1 and 2 (SNAI1 and SNAI2), Zinc Finger E-Box Binding Homeobox 1 and 2 (ZEB1 and ZEB2), and the down-regulation, among others, of members of the miR-200 family involved in the maintenance of an epithelial phenotype. Subsequent differentiation to different types of mesenchymal tissues increases tumor heterogeneity and probably modulates clinical behavior and therapy response.MDPI2020202020192020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion21 p.application/pdfhttps://hdl.handle.net/2445/171362Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3390/cancers11070964Cancers, 2019, vol. 11, num. 7https://doi.org/10.3390/cancers11070964cc by (c) Leskela et al., 2019http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1713622026-05-29T05:05:01Z
dc.title.none.fl_str_mv Molecular Basis of Tumor Heterogeneity in Endometrial Carcinosarcoma
title Molecular Basis of Tumor Heterogeneity in Endometrial Carcinosarcoma
spellingShingle Molecular Basis of Tumor Heterogeneity in Endometrial Carcinosarcoma
Leskela, Susanna
Càncer d'endometri
Expressió gènica
Endometrial cancer
Gene expression
title_short Molecular Basis of Tumor Heterogeneity in Endometrial Carcinosarcoma
title_full Molecular Basis of Tumor Heterogeneity in Endometrial Carcinosarcoma
title_fullStr Molecular Basis of Tumor Heterogeneity in Endometrial Carcinosarcoma
title_full_unstemmed Molecular Basis of Tumor Heterogeneity in Endometrial Carcinosarcoma
title_sort Molecular Basis of Tumor Heterogeneity in Endometrial Carcinosarcoma
dc.creator.none.fl_str_mv Leskela, Susanna
Pérez Mies, Belén
Rosa Rosa, Juan Manuel
Cristobal, Eva
Biscuola, Michele
Palacios Berraquero, María L.
Ong, SuFey
Matias-Guiu, Xavier, 1958-
Palacios, José
author Leskela, Susanna
author_facet Leskela, Susanna
Pérez Mies, Belén
Rosa Rosa, Juan Manuel
Cristobal, Eva
Biscuola, Michele
Palacios Berraquero, María L.
Ong, SuFey
Matias-Guiu, Xavier, 1958-
Palacios, José
author_role author
author2 Pérez Mies, Belén
Rosa Rosa, Juan Manuel
Cristobal, Eva
Biscuola, Michele
Palacios Berraquero, María L.
Ong, SuFey
Matias-Guiu, Xavier, 1958-
Palacios, José
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer d'endometri
Expressió gènica
Endometrial cancer
Gene expression
topic Càncer d'endometri
Expressió gènica
Endometrial cancer
Gene expression
description Endometrial carcinosarcoma (ECS) represents one of the most extreme examples of tumor heterogeneity among human cancers. ECS is a clinically aggressive, high-grade, metaplastic carcinoma. At the morphological level, intratumor heterogeneity in ECS is due to an admixture of epithelial (carcinoma) and mesenchymal (sarcoma) components that can include heterologous tissues, such as skeletal muscle, cartilage, or bone. Most ECSs belong to the copy-number high serous-like molecular subtype of endometrial carcinoma, characterized by the TP53 mutation and the frequently accompanied by a large number of gene copy-number alterations, including the amplification of important oncogenes, such as CCNE1 and c-MYC. However, a proportion of cases (20%) probably represent the progression of tumors initially belonging to the copy-number low endometrioid-like molecular subtype (characterized by mutations in genes such as PTEN, PI3KCA, or ARID1A), after the acquisition of the TP53 mutations. Only a few ECS belong to the microsatellite-unstable hypermutated molecular type and the POLE-mutated, ultramutated molecular type. A common characteristic of all ECSs is the modulation of genes involved in the epithelial to mesenchymal process. Thus, the acquisition of a mesenchymal phenotype is associated with a switch from E- to N-cadherin, the up-regulation of transcriptional repressors of E-cadherin, such as Snail Family Transcriptional Repressor 1 and 2 (SNAI1 and SNAI2), Zinc Finger E-Box Binding Homeobox 1 and 2 (ZEB1 and ZEB2), and the down-regulation, among others, of members of the miR-200 family involved in the maintenance of an epithelial phenotype. Subsequent differentiation to different types of mesenchymal tissues increases tumor heterogeneity and probably modulates clinical behavior and therapy response.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/171362
url https://hdl.handle.net/2445/171362
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/cancers11070964
Cancers, 2019, vol. 11, num. 7
https://doi.org/10.3390/cancers11070964
dc.rights.none.fl_str_mv cc by (c) Leskela et al., 2019
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Leskela et al., 2019
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 21 p.
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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