Mark W. Zimmerman, PhD (Damon Runyon-Sohn Fellow ’14-’18) and colleagues at the Dana-Farber Cancer Institute, Boston, have identified mechanisms that drive about 10 percent of high-risk neuroblastoma cases. Neuroblastoma is the most common solid tumor affecting infants and young children with few effective treatment options. The researchers found that a protein called c-MYC could cause neuroblastoma, when it is produced at abnormally high levels in tumor cells in a zebrafish model. They also found that chromosomes had breaks and rearrangements near the gene producing c-MYC. Such rearrangements put c-MYC next to pieces of DNA called super-enhancers that normally regulate and increase expression of other genes. c-MYC hijacked the super-enhancers, driving the development of neuroblastoma. This offers a new focus for precision drug development, particularly for an emerging class of drugs that work by degrading proteins like c-MYC. The results were published in Cancer Discovery.
