Study Title: The KAT module of the SAGA complex maintains the oncogenic gene expression program in MYCN-amplified neuroblastoma
Publication: Science Advances
Dana-Farber Cancer Institute authors: Clare F. Malone, PhD; Nathaniel W. Mabe, PharmD, PhD; Kimberly Stegmaier, MD
Summary:
Researchers at Dana-Farber Cancer Institute have identified a protein complex that is required for the growth of a high-risk form of childhood brain cancer called MYCN-amplified neuroblastoma. The MYCN gene is amplified in approximately 20-25% of childhood neuroblastoma cases. MYCN produces a transcription factor called MYCN that turns on a cancer-driving gene expression program. Suppressing this oncogenic program by inhibiting MYCN directly is difficult, so this team used functional genomic screens to identify other potential ways to suppress the program. They discovered that expression of the MYCN program depends on the SAGA complex, which is an epigenetic regulator. They also found that the SAGA complex can be inhibited pharmacologically, making it an attractive potential target for future drug development in neuroblastoma.
Significance:
Neuroblastoma is the most common childhood solid tumor and accounts for a disproportionately high number of cancer-related deaths in children. This research identifies a potential novel approach to treatment of MYCN-amplified neuroblastoma, a high-risk form of the disease which accounts for approximately 20-25% of childhood neuroblastoma cases.
Funding:
Helen Gurley Brown Presidential Initiative, National Institutes of Health, V Foundation, and Friends for Life
