Characterization of a Preclinical In Vitro Model Derived from a SMARCA4-Mutated Sinonasal Teratocarcinosarcoma
Sinonasal teratocarcinosarcoma (TCS) is a rare tumor that displays a variable histology with admixtures of epithelial, mesenchymal, neuroendocrine and germ cell elements. Facing a very poor prognosis, patients with TCS are in need of new options for treatment. Recently identified recurrent mutations...
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MDPI AG
2023-12-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/13/1/81 |
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| author | Sara Lucila Lorenzo-Guerra Helena Codina-Martínez Laura Suárez-Fernández Virginia N. Cabal Rocío García-Marín Cristina Riobello Blanca Vivanco Verónica Blanco-Lorenzo Paula Sánchez-Fernández Fernando López Jóse Luis Llorente Mario A. Hermsen |
| author_facet | Sara Lucila Lorenzo-Guerra Helena Codina-Martínez Laura Suárez-Fernández Virginia N. Cabal Rocío García-Marín Cristina Riobello Blanca Vivanco Verónica Blanco-Lorenzo Paula Sánchez-Fernández Fernando López Jóse Luis Llorente Mario A. Hermsen |
| author_sort | Sara Lucila Lorenzo-Guerra |
| collection | DOAJ |
| description | Sinonasal teratocarcinosarcoma (TCS) is a rare tumor that displays a variable histology with admixtures of epithelial, mesenchymal, neuroendocrine and germ cell elements. Facing a very poor prognosis, patients with TCS are in need of new options for treatment. Recently identified recurrent mutations in <i>SMARCA4</i> may serve as target for modern therapies with EZH1/2 and CDK4/6 inhibitors. Here, we present the first in vitro cell line TCS627, established from a previously untreated primary TCS originating in the ethmoid sinus with invasion into the brain. The cultured cells expressed immunohistochemical markers, indicating differentiation of epithelial, neuroepithelial, sarcomatous and teratomatous components. Whole-exome sequencing revealed 99 somatic mutations including <i>SMARCA4</i>, <i>ARID2</i>, <i>TET2</i>, <i>CDKN2A</i>, <i>WNT7A</i>, <i>NOTCH3</i> and <i>STAG2</i>, all present both in the primary tumor and in the cell line. Focusing on mutated <i>SMARCA4</i> as the therapeutic target, growth inhibition assays showed a strong response to the CDK4/6 inhibitor palbociclib, but much less to the EZH1/2 inhibitor valemetostat. In conclusion, cell line TCS627 carries both histologic and genetic features characteristic of TCS and is a valuable model for both basic research and preclinical testing of new therapeutic options for treatment of TCS patients. |
| first_indexed | 2024-03-08T15:09:32Z |
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| id | doaj.art-9590abd8cef941b5bed520111ef202d9 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-08T15:09:32Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-9590abd8cef941b5bed520111ef202d92024-01-10T14:53:27ZengMDPI AGCells2073-44092023-12-011318110.3390/cells13010081Characterization of a Preclinical In Vitro Model Derived from a SMARCA4-Mutated Sinonasal TeratocarcinosarcomaSara Lucila Lorenzo-Guerra0Helena Codina-Martínez1Laura Suárez-Fernández2Virginia N. Cabal3Rocío García-Marín4Cristina Riobello5Blanca Vivanco6Verónica Blanco-Lorenzo7Paula Sánchez-Fernández8Fernando López9Jóse Luis Llorente10Mario A. Hermsen11Department of Head and Neck Cancer, Health Research Institute of the Principality of Asturias, 33011 Oviedo, SpainDepartment of Head and Neck Cancer, Health Research Institute of the Principality of Asturias, 33011 Oviedo, SpainDepartment of Head and Neck Cancer, Health Research Institute of the Principality of Asturias, 33011 Oviedo, SpainDepartment of Head and Neck Cancer, Health Research Institute of the Principality of Asturias, 33011 Oviedo, SpainDepartment of Head and Neck Cancer, Health Research Institute of the Principality of Asturias, 33011 Oviedo, SpainDepartment of Head and Neck Cancer, Health Research Institute of the Principality of Asturias, 33011 Oviedo, SpainDepartment of Pathology, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainDepartment of Pathology, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainDepartment of Otolaryngology, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainDepartment of Otolaryngology, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainDepartment of Otolaryngology, Hospital Universitario Central de Asturias, 33011 Oviedo, SpainDepartment of Head and Neck Cancer, Health Research Institute of the Principality of Asturias, 33011 Oviedo, SpainSinonasal teratocarcinosarcoma (TCS) is a rare tumor that displays a variable histology with admixtures of epithelial, mesenchymal, neuroendocrine and germ cell elements. Facing a very poor prognosis, patients with TCS are in need of new options for treatment. Recently identified recurrent mutations in <i>SMARCA4</i> may serve as target for modern therapies with EZH1/2 and CDK4/6 inhibitors. Here, we present the first in vitro cell line TCS627, established from a previously untreated primary TCS originating in the ethmoid sinus with invasion into the brain. The cultured cells expressed immunohistochemical markers, indicating differentiation of epithelial, neuroepithelial, sarcomatous and teratomatous components. Whole-exome sequencing revealed 99 somatic mutations including <i>SMARCA4</i>, <i>ARID2</i>, <i>TET2</i>, <i>CDKN2A</i>, <i>WNT7A</i>, <i>NOTCH3</i> and <i>STAG2</i>, all present both in the primary tumor and in the cell line. Focusing on mutated <i>SMARCA4</i> as the therapeutic target, growth inhibition assays showed a strong response to the CDK4/6 inhibitor palbociclib, but much less to the EZH1/2 inhibitor valemetostat. In conclusion, cell line TCS627 carries both histologic and genetic features characteristic of TCS and is a valuable model for both basic research and preclinical testing of new therapeutic options for treatment of TCS patients.https://www.mdpi.com/2073-4409/13/1/81sinonasal cancerteratocarcinosarcomain vitro modelexome sequencingSMARCA4 mutationpreclinical drug testing |
| spellingShingle | Sara Lucila Lorenzo-Guerra Helena Codina-Martínez Laura Suárez-Fernández Virginia N. Cabal Rocío García-Marín Cristina Riobello Blanca Vivanco Verónica Blanco-Lorenzo Paula Sánchez-Fernández Fernando López Jóse Luis Llorente Mario A. Hermsen Characterization of a Preclinical In Vitro Model Derived from a SMARCA4-Mutated Sinonasal Teratocarcinosarcoma Cells sinonasal cancer teratocarcinosarcoma in vitro model exome sequencing SMARCA4 mutation preclinical drug testing |
| title | Characterization of a Preclinical In Vitro Model Derived from a SMARCA4-Mutated Sinonasal Teratocarcinosarcoma |
| title_full | Characterization of a Preclinical In Vitro Model Derived from a SMARCA4-Mutated Sinonasal Teratocarcinosarcoma |
| title_fullStr | Characterization of a Preclinical In Vitro Model Derived from a SMARCA4-Mutated Sinonasal Teratocarcinosarcoma |
| title_full_unstemmed | Characterization of a Preclinical In Vitro Model Derived from a SMARCA4-Mutated Sinonasal Teratocarcinosarcoma |
| title_short | Characterization of a Preclinical In Vitro Model Derived from a SMARCA4-Mutated Sinonasal Teratocarcinosarcoma |
| title_sort | characterization of a preclinical in vitro model derived from a smarca4 mutated sinonasal teratocarcinosarcoma |
| topic | sinonasal cancer teratocarcinosarcoma in vitro model exome sequencing SMARCA4 mutation preclinical drug testing |
| url | https://www.mdpi.com/2073-4409/13/1/81 |
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