AT-08: OVEREXPRESSION OF TEAD4 IN AT/RT; NEW INSIGHT TO THE PATHOPHYSIOLOGY OF AN AGGRESSIVE BRAIN TUMOR

BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant brain tumor that occurs in early childhood. It comprises 1-2% of all pediatric brain tumors. About 20% of the patients are younger than three years old at the time of diagnosis. Although most of tumors are characterized by inactivation of SMARCB1 tumor-suppressor gene, much of the biological contribution to the development and aggressiveness of this tumor is still poorly understood. We aim to investigate new molecular pathways involved in AT/RT formation and progression. MATERIALS AND METHODS: Tumor samples were collected from patients diagnosed with AT/RT. Copy number variation (CNV) study was performed to investigate the character in one patient using primary and relapsed tumors. The data was verified in a large set of samples by gene expression analysis, quantitative real-time PCR, and immunohistochemistry. RESULTS: Amplification of TEAD4 was observed by CNV study and in situ hybridization. In a large set of samples, expression of TEAD4 and its co-activator YAP1 were significantly higher in AT/RT when compared with medulloblastoma. TEAD4 protein was expressed mostly in nuclei and YAP1 was both nuclei and cytoplasm of tumor cells. MYC and CCND1, downstream targets of Hippo pathway, were also overexpressed at mRNA and protein levels. CONCLUSION: Here we report the overexpression of TEAD4 and YAP1 in AT/RT, both of which are key components of Hippo pathway, which plays an important role in tumor development. Our results may represent new insight to the pathophysiology on AT/RT.