St. Baldrick’s Researcher Discovers Gene Mutations Linked with High-Risk Neuroblastoma

By Michael Hogarty, M.D., St. Baldrick’s Research Grant Recipient, Children’s Hospital of Philadelphia

Five years ago at a childhood cancer conference, I sat next to someone who would significantly impact the childhood cancer research I am doing today. She was a St. Baldrick’s staff member who listened as I lamented that the National Institutes of Health (NIH) wasn’t interested in funding genomic sequencing of childhood cancers. At that time the NIH was only supporting whole genome sequencing for common adult cancers, like breast and colon cancer, as this new technology was especially expensive and resource-intensive. She smiled, introduced herself, and told me that this was exactly the kind of research the St. Baldrick’s Foundation wanted to fund- important pediatric cancer studies that were not considered a funding priority at the national level- and encouraged me to apply for a grant from their foundation.

Today, thanks to over $1 million in funding from St. Baldrick’s, as well as support from the Children’s Oncology Group and collaborators at the Children’s Hospital of Philadelphia, John Hopkins University and Texas Tech, we have been able to conduct a pediatric cancer genome sequencing project focused on high-risk neuroblastomas. When this project was initiated it was the first of its kind to solely sequence a common childhood tumor. This type of research is important because when we sequence tumors and catalogue the DNA mutations which cause the cancer we begin to better understand the enemy. Ultimately our goal is to use this information to make better and more effective treatment decisions.

Our team has identified DNA mutations in two genes in aggressive neuroblastomas. ARID1A and ARID1B gene mutations were discovered in 11% of the neuroblastomas studied, and sadly almost all children with mutations in one of these genes had very aggressive tumors that were not curable with current treatments. These findings are exciting because they could serve as the foundation to identify novel treatment types and predict outcomes for such highest risk patients. Importantly, we discovered that the expression of many of the genes that work alongside ARID1A and ARID1B also correlate with poor patient outcome, so it seems that whatever this group of genes is doing in the cells is important.

Our next step is to validate these findings in a larger set of tumors to better understand just how often these mutations occur in neuroblastomas of different stages and in children of different ages. We also plan to look at how these gene mutations affect the growth of the tumor cells and whether there are certain vulnerabilities these cells might have. In the years to come, our team hopes to discover whether this new insight might open up novel treatment options for children with the ARID1A and ARID1B mutations in their tumors.

We need to continue to push for cutting-edge research for childhood cancers – particularly in the setting of ongoing reductions in cancer research funding from NIH – it’s the only way we will make the progress these children deserve. I extend my deepest thanks, and those of our extended research team, to the supporters of the St. Baldrick’s Foundation. Without you, this project, and these findings, would never have happened.

Make a donation to fund life-saving childhood cancer research, or read about the most recent round of St. Baldrick’s childhood cancer research grants.