Comparative analysis of RNA expression in a single institution cohort of pediatric cancer patients.

With the low incidence of mutations in pediatric cancers, alternate genomic approaches are needed to identify therapeutic targets. Our study, the Comparative Analysis of RNA Expression to Improve Pediatric and Young Adult Cancer Treatment, was conducted by the UC Santa Cruz Treehouse Childhood Cancer Initiative and Stanford University School of Medicine. RNA sequencing data from 33 children and young adults with a relapsed, refractory or rare cancer underwent CARE analysis to reveal activated cancer driver pathways and nominate treatments. We compare our pipeline to other gene expression outlier detection approaches and discuss challenges for clinical implementation. Of our 33 patients, 31 (94%) had findings of potential clinical significance. Findings were implemented in 5 patients, 3 of which had defined clinical benefit. We demonstrate that comparator cohort composition determines which outliers are detected. This study highlights the clinical utility and challenges of implementing comparative RNA sequencing analysis in the clinic.