Abstract 26P
Background
Sinonasal teratocarcinomas (SNTCS) are very rare and highly aggressive tumors. Histologically they display mixed epithelial, mesenchymal, and neuroendocrine components. Recent genetic studies indicated recurrent alterations in genes SMARCA4, SALL-4 and CTNNB1. No effective pharmacological therapy is currently available, partly due to a lack of experimental models for studying the pathobiology and drug responsiveness of this tumor. Our aim was to set up and characterize an in vitro model of this tumor type.
Methods
A cell line named TCS627 was established from a 68-year-old man with a previously untreated, primary stage T4 SNTCS originating in the ethmoid sinus with invasion into the brain. Both primary tumor and cell line were histopathologically characterized using immunohistochemical markers, and genetically by whole exome sequencing (WES).
Results
The primary tumor showed epithelial, mesenchymal, neuroendocrine and germ cell histological features and expressed diagnostic markers CK8, S-100, enolase and SALL4, respectively. TCS627 grew in various proportions of cuboid, fusiform and small round cells with scant cytoplasm, dependent on population density and culture medium conditions. TCS627 cells expressed the same histological markers as its corresponding primary tumor. Population doubling time was 48 hours. The cell line had a predominant tetraploid karyotype with copy number loss at 1p and gains at 1q and 12p. WES revealed somatic frameshift mutations in ARID2 and CDKN2A, splicing mutations in SATB2 and SMARCA4, and missense mutations in NOTCH3, STAG2 and TET2, both in the primary tumor and the cell line. SMARCA4 protein expression was lost in the cell line but not in the primary tumor. CTNNB1 mutation or nuclear β-catenin staining was not observed.
Conclusions
To our knowledge, this is the first report of an in vitro model of SNTCS. It expresses epithelial, mesenchymal, neuroendocrine and germ cell markers and harbours the previously described chromosomal gains and losses, as well as SMARCA4 mutation. Therefore, TCS627 constitutes a useful tool for testing new therapeutic approaches for SNTCS.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The author.
Funding
Instituto de Salud Carlos III grant PI19/00191.
Disclosure
The author has declared no conflicts of interest.