Establishment of Salivary Gland Tumors Arising in Salivary Gland‐Specific <i>EWSR1::ATF1</i> Transgenic Mice

BACKGROUND: Salivary gland carcinomas are uncommon malignancies with various histological subtypes harboring fusion genes. The EWSR1::ATF1 fusion gene, resulting from a translocation between chromosomes 12 and 22, is frequently observed in hyalinizing clear cell carcinoma (HCCC). However, the role of this fusion gene in HCCC oncogenesis remains unclear. METHODS: We generated EWSR1::ATF1 transgenic mice by introducing an EWSR1::ATF1 fusion gene with a breakpoint in HCCC. These mice were crossed with Lama parotid secretory protein (PSP)-Cre transgenic mice, expressing Cre recombinase in salivary glands, to produce salivary gland-specific EWSR1::ATF1 transgenic mice. Tumor samples were analyzed using Western blotting, histopathology, and RNA sequencing. RESULTS: We generated salivary gland-specific EWSR1::ATF1 transgenic mice, and tumors developed in major salivary glands in three mice. These tumors exhibited more malignant characteristics than human HCCC. CONCLUSIONS: These results suggest that salivary gland-specific expression of EWSR1::ATF1 plays an important role in malignant tumor formation in major salivary glands.