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Determining the Impact of Regulatory Mutations and Dysregulated Transcription Factors in Neuroblastoma

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Brain Cancer

Pediatric Cancer

Graham McVicker (Salk)

Peter Zage (UCSD/Rady)

Neuroblastoma is a tumor of developmental origin with high incidence of metastatic disease at initial diagnosis. Comprehensive DNA sequencing of high-risk neuroblastoma has identified few clinically actionable gene mutations and precision medicine has not benefited most neuroblastoma patients. Thus, there is an urgent need to develop innovative approaches to discover novel cancer dependencies and gene targets in neuroblastoma. Recently, we used DNA and RNA sequencing data to discover recurrently dysregulated genes in neuroblastoma. This proposal will use new molecular experiments to determine how genetic mutations affect gene expression, and downstream molecular pathways in neuroblastoma tumors. Discovering causes of aberrant gene expression in neuroblastomas is important because cancer cell identity is determined by gene expression, and gene expression influences important oncogenic processes like tumor growth and metastasis. The main objective of this proposal is to discover novel genetic mutations and cancer genes and determine their impact on neuroblastoma tumorigenesis. The long-term objective of this project is to discover prognostic biomarkers and therapeutic targets for early detection and treatment of neuroblastoma.

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