Identification of a new target for childhood neuroblastoma: study

Study title: The KAT module of the SAGA complex maintains the oncogenic gene expression program in MYCN-amplified neuroblastoma

Publication: Scientific advances

Authors from Dana-Farber Cancer Institute: Clare F. Malone, PhD; Nathaniel W. Mabe, PharmD, PhD; Kimberly Stegmaier, MD

Summary:

Dana-Farber Cancer Institute researchers have identified a protein complex necessary for the growth of a high-risk form of childhood brain cancer called MYCN-amplified neuroblastoma. The MYCN gene is amplified in approximately 20 to 25% of cases of childhood neuroblastoma. MYCN produces a transcription factor called MYCN that activates a gene expression program responsible for cancer. It is difficult to suppress this oncogenic program by directly inhibiting MYCN. This team therefore used functional genomic screens to identify other potential ways to suppress the program. They discovered that the expression of the MYCN program depends on the SAGA complex, which is an epigenetic regulator. They also discovered that the SAGA complex can be inhibited pharmacologically, making it an attractive potential target for future neuroblastoma drug development.

Importance:

Neuroblastoma is the most common childhood solid tumor and accounts for a disproportionate number of cancer-related deaths in children. This research identifies a potential new approach for the treatment of MYCN-amplified neuroblastoma, a high-risk form of the disease that 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