| Autor: |
Lorenzo-Guerra SL; Department of Head and Neck Cancer, Health Research Institute of the Principality of Asturias, 33011 Oviedo, Spain., Codina-Martínez H; Department of Head and Neck Cancer, Health Research Institute of the Principality of Asturias, 33011 Oviedo, Spain., Suárez-Fernández L; Department of Head and Neck Cancer, Health Research Institute of the Principality of Asturias, 33011 Oviedo, Spain., Cabal VN; Department of Head and Neck Cancer, Health Research Institute of the Principality of Asturias, 33011 Oviedo, Spain., García-Marín R; Department of Head and Neck Cancer, Health Research Institute of the Principality of Asturias, 33011 Oviedo, Spain., Riobello C; Department of Head and Neck Cancer, Health Research Institute of the Principality of Asturias, 33011 Oviedo, Spain., Vivanco B; Department of Pathology, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain., Blanco-Lorenzo V; Department of Pathology, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain., Sánchez-Fernández P; Department of Otolaryngology, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain., López F; Department of Otolaryngology, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain., Llorente JL; Department of Otolaryngology, Hospital Universitario Central de Asturias, 33011 Oviedo, Spain., Hermsen MA; Department of Head and Neck Cancer, Health Research Institute of the Principality of Asturias, 33011 Oviedo, Spain. |
| Abstrakt: |
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 SMARCA4 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 SMARCA4 , ARID2 , TET2 , CDKN2A , WNT7A , NOTCH3 and STAG2 , all present both in the primary tumor and in the cell line. Focusing on mutated SMARCA4 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. |
