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The Role of ARID1A in Neuroblastoma Pathogenesis

Dana-Farber Cancer Institute
Hui Shi, PhD
Grant Type: 
Young Investigator Grants
Year Awarded: 
Type of Childhood Cancer: 
Project Description: 


Neuroblastoma is a solid tumor of the peripheral sympathetic nervous system (PSNS) in children. It is difficult to treat in many of the children with high-risk disease and accounts for 15% of childhood cancer deaths. MYCN amplification is present in approximately 20-25% of neuroblastomas and has been the most common genetic aberration that is associated with poor prognosis in neuroblastoma. A tumor suppressor gene called ARID1A is inactivated by mutation and deletion in neuroblastoma tumors from up to one third of children with very high-risk neuroblastoma and also in adult tumors, such as ovarian cancer and endometrial tumors. 

Project Goal

I have created the first zebrafish model of ARID1A inactivation and my preliminary data has shown that loss of ARID1A dramatically accelerates the onset and increases the penetrance of MYCN-induced neuroblastoma. Thus, my fish model provides the ideal system to study the mechanism of the loss of ARID1A in tumorigenesis. My novel work is highly likely to result in improved targeted treatments for high-risk neuroblastoma, as well as for other human tumors such as ovarian and endometrial tumors that also exhibit loss of the ARID1A tumor suppressor gene.

"With the support from Alex's Lemonade Stand Foundation, I will be able to continue focusing my efforts on studying the role of ARID1A in neuroblastoma pathogenesis in zebrafish model system. As a component of an important chromatin remodeling complex, loss of function of ARID1A will probably affect the transcription of genes that are required to suppress tumorigenesis. Since this epigenetic alteration is potentially reversible, we can develop novel drugs for neuroblastoma with mutation in ARID1A. I am grateful for this funding from ALSF because it will also help me to move forward to become an independent principal investigator in pediatric oncology." - Hui Shi, PhD