New Insight into Biology of Aggressive Brain Tumor

Atypical teratoid/rhabdoid tumor (AT/RT) is a highly aggressive brain tumor that occurs mainly in early childhood. The prognosis for many patients with AT/RT is poor, and the biological basis of its tumorigenesis and aggressiveness is still unknown.

The laboratory of Simone Treiger Sredni, MD, PhD, published an article in Pediatric Blood and Cancer that identified a gene that had not been previously implicated in AT/RT. This discovery helps to clarify the aggressiveness of this tumor. The team developed primary cell lines generated from a patient’s tumors. They analyzed the cell lines to identify genes involved in AT/RT biology. The expression of one of these genes – TEA domain family member 4 (TEAD4) – was validated in AT/RT patient samples.

 TEAD4 functions as part of a signaling pathway that, when properly regulated, plays an important role in tumor suppression. The team investigated the function of TEAD4 in rhabdoid tumor cells, including amplification and overexpression – which may lead to cell proliferation and cancer aggressiveness. TEAD4 amplification was detected in the primary cell lines and its overexpression was confirmed at mRNA and protein levels in an independent cohort of AT/RT samples. TEAD4’s co-activator, YAP1, and two downstream targets, were also found to be upregulated in AT/RT when compared to a closely related type of tumor that shows better outcomes for patients, medulloblastoma. Cell proliferation and migration were significantly reduced in TEAD4 cells that had been mutated.

Overall, the results from this study suggest that TEAD4 plays a role in the pathophysiology of AT/RT, which represents a new insight into the biology of this aggressive tumor. Research scholar Mario Suzuki, MD, was first author. Sredni is a member of the Cancer Biology and Epigenomics Program​ of the Manne Research Institute and Research Associate Professor of Neurological Surgery​ at Northwestern University Feinberg School of Medicine.​​

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