Molecular Basis of Tumor Heterogeneity in Endometrial Carcinosarcoma

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2019Author
Leskelä, Susanna
Pérez-Mies, Belén
Rosa-Rosa, Juan Manuel
Cristobal, Eva
Biscuola, Michele
Palacios-Berraquero, María L.
Ong, SuFey
Palacios, José
Suggested citation
Leskelä, Susanna;
Pérez-Mies, Belén;
Rosa-Rosa, Juan Manuel;
Cristobal, Eva;
Biscuola, Michele;
Palacios-Berraquero, María L.;
...
Palacios, José.
(2019)
.
Molecular Basis of Tumor Heterogeneity in Endometrial Carcinosarcoma.
Cancers, 2019, vol. 11, núm. 7, article number 964.
https://doi.org/10.3390/cancers11070964.
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Show full item recordAbstract
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.
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Cancers, 2019, vol. 11, núm. 7, article number 964European research projects
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