Identification of TFAP4 (Transcription Factor AP-4/Activating Enhancer Binding Protein) as a Potential Master Regulator/Synthetic Lethal Gene of MYCN Amplified Neuroblastoma
Amplification of oncogene MYCN is a hallmark of neuroblastoma, and is associated with metastasis and very poor survival. However, despite the identification of MYCN-amplification as an adverse prognostic marker, no drugs that target MYCN have been developed.
As an alternative approach to targeting MYCN, we have identified genes that are essential for the growth of MYCN-amplified tumors. In particular, we have found that turning off the expression of the transcription factor TFAP4, inhibits the growth of neuroblastoma cells. We plan to turn off the expression of TFAP4 in mouse tumors. We will also plan to determine what genes cooperate with TFAP4 in making for aggressive, poor-prognosis neuroblastoma. Ultimately, we hope to find drugs that target TFAP4 and the cooperating genes, in order to improve the outcome of children with neuroblastoma.