Experimental Models of Sinonasal Tumors for Preclinical Testing of Candidate Targeted Therapies

Codina-Martínez, Helena; Lorenzo-Guerra, Sara Lucila; Cabal, Virginia N.; García-Marín, Rocío; Riobello, Cristina; Suárez-Fernández, Laura; Vivanco, Blanca; Blanco-Lorenzo, Verónica; López, Fernando; Sánchez-Fernández, Paula; Hermsen, Mario A.; Llorente, José Luis

doi:10.1007/s40136-023-00496-9

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“…Recently identified recurrent mutations in SWI/SNF and Wnt pathway related genes [ 18 , 19 , 20 , 22 , 24 , 25 ] may serve as targets for modern therapies with specific inhibitors, but preclinical development and testing of new compounds is hampered by the lack of appropriate experimental models. This is particularly the case for rare malignancies such as sinonasal tumors, of which only few cell lines have been established [ 37 ]. To our knowledge, TCS627 is the first in vitro model for sinonasal TCS to be described in the scientific literature.…”

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confidence: 99%

Characterization of a Preclinical In Vitro Model Derived from a SMARCA4-Mutated Sinonasal Teratocarcinosarcoma

Lorenzo-Guerra,

Codina-Martínez,

Suárez-Fernández

et al. 2023

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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.

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