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: Leskelä, Susanna, Pérez-Mies, Belén, Rosa-Rosa, Juan Manuel, Cristobal, Eva, Biscuola, Michele, Palacios-Berraquero, María L., Ong, SuFey, Matias-Guiu, Xavier, Palacios, José
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universitat de Lleida (UdL)
Repositorio:Repositori Obert UdL
OAI Identifier:oai:repositori.udl.cat:10459.1/68211
Acceso en línea:https://doi.org/10.3390/cancers11070964
http://hdl.handle.net/10459.1/68211
Access Level:acceso abierto
Palabra clave:Uterine carcinosarcoma
Endometrial carcinoma
Metaplastic carcinoma
Epithelial-tomesenchymal transition
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spelling Molecular Basis of Tumor Heterogeneity in Endometrial CarcinosarcomaLeskelä, SusannaPérez-Mies, BelénRosa-Rosa, Juan ManuelCristobal, EvaBiscuola, MichelePalacios-Berraquero, María L.Ong, SuFeyMatias-Guiu, XavierPalacios, JoséUterine carcinosarcomaEndometrial carcinomaMetaplastic carcinomaEpithelial-tomesenchymal transitionEndometrial 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.This review was funded by grants from the Instituto de Salud Carlos III (ISCIII) (PIE15/00050 and PI16/00887) and CIBERONC (CB16/12/00316 and CB16/12/00231, CB16/12/00361), co-financed by the European Development Regional Fund. ‘A way to achieve Europe’ (FEDER), and by the Spanish Association Against Cancer Scientific Foundation (grants: AIO-aecc 2016 and Grupos Coordinados Traslacionales aecc 2018).MDPI2019info:eu-repo/semantics/articlehttps://doi.org/10.3390/cancers11070964http://hdl.handle.net/10459.1/68211reponame:Repositori Obert UdL instname:Universitat de Lleida (UdL)InglésReproducció del document publicat a https://doi.org/10.3390/cancers11070964Cancers, 2019, vol. 11, núm. 7, article number 964cc-by, (c) Leskela et al., 2019info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/oai:repositori.udl.cat:10459.1/682112026-06-24T12:42:17Z
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
Leskelä, Susanna
Uterine carcinosarcoma
Endometrial carcinoma
Metaplastic carcinoma
Epithelial-tomesenchymal transition
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 Leskelä, Susanna
Pérez-Mies, Belén
Rosa-Rosa, Juan Manuel
Cristobal, Eva
Biscuola, Michele
Palacios-Berraquero, María L.
Ong, SuFey
Matias-Guiu, Xavier
Palacios, José
author Leskelä, Susanna
author_facet Leskelä, Susanna
Pérez-Mies, Belén
Rosa-Rosa, Juan Manuel
Cristobal, Eva
Biscuola, Michele
Palacios-Berraquero, María L.
Ong, SuFey
Matias-Guiu, Xavier
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
Palacios, José
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Uterine carcinosarcoma
Endometrial carcinoma
Metaplastic carcinoma
Epithelial-tomesenchymal transition
topic Uterine carcinosarcoma
Endometrial carcinoma
Metaplastic carcinoma
Epithelial-tomesenchymal transition
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
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://doi.org/10.3390/cancers11070964
http://hdl.handle.net/10459.1/68211
url https://doi.org/10.3390/cancers11070964
http://hdl.handle.net/10459.1/68211
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, núm. 7, article number 964
dc.rights.none.fl_str_mv cc-by, (c) Leskela et al., 2019
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
rights_invalid_str_mv cc-by, (c) Leskela et al., 2019
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositori Obert UdL
instname:Universitat de Lleida (UdL)
instname_str Universitat de Lleida (UdL)
reponame_str Repositori Obert UdL
collection Repositori Obert UdL
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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