Establishment of Salivary Gland Tumors Arising in Salivary Gland-Specific EWSR1::ATF1 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.