Precision oncology relies on the identification of targetable driver mutations. However, based on our current coding-focused understanding of the cancer genome, many paediatric cancers seem to lack driver mutations entirely. We hypothesise that the apparent low rate of driver mutations in some paediatric cancers is due to present-day limitations in interpreting synonymous and noncoding variation (SNCV).
What are the goals of this project?
The goals of this project are to investigate the prevalence and functional impact of somatic SNCV on splicing, promoter activity, and enhancer hijacking and to investigate the prevalence and functional impact of genomic insertion of somatic mobile elements and viruses.
What is the impact of this project?
High-risk paediatric cancers have dismal survival rates, and despite best efforts using advanced DNA sequencing, we find very few mutations to explain this aggressiveness. We reasoned that whole classes of under-explored mutations in the "noncoding genome" may explain their poor outcomes, and we propose innovative ways to study these in the largest study of patients with these cancers to date.
The Children's Brain Tumor Network contributed to this project by providing access to the Pediatric Brain Tumor Atlas
PI: Mark Cowley
Adam Resnick, PhD
Adam Resnick is the Director of Data Driven Discovery in Biomedicine (D3b) at Children’s Hospital of Philadelphia (CHOP) responsible for leading a multidisciplinary team to build and support a scalable, patient-focused healthcare and educational discovery ecosystem on behalf of all children. He i
Children’s Hospital of Philadelphia