Comparative RNA Expression in Pediatric Cancers: A New Tool for Precision Medicine

This study from the UC Santa Cruz Treehouse Childhood Cancer Initiative and Stanford University School of Medicine demonstrates the clinical potential of Comparative Analysis of RNA Expression (CARE) in pediatric and young adult cancers—especially when DNA mutations alone aren't enough to guide treatment. 

🎯 Objective 

To evaluate whether RNA-Seq analysis can identify clinically actionable targets in pediatric patients with relapsed, refractory, or rare tumors, and compare the CARE pipeline with other gene expression outlier detection strategies. 

🧒 Study Overview 

• 33 patients (median age: 11 years, range 0–24) 
• Diagnoses included soft tissue sarcomas (48%), among others 
• RNA-Seq performed on tumor samples + DNA mutation panel 
• Average turnaround: 20 days 

🔍 Key Findings 

1. High Detection Rate 

• 31 of 33 patients (94%) had clinically relevant molecular findings 
• 89 gene expression outliers were identified, 79% via automated CARE pipeline, 21% via manual curation 

1. Treatment Impact 

• CARE findings were used in treatment of 5 patients 
• 3 patients benefited with either stable disease or full remission 

1. Comparator Cohort Matters 

• Outlier results varied depending on which reference cohort was used 
• TCGA alone (mostly adult samples) produced pediatric-irrelevant outliers 
• Personalized, disease-specific cohorts gave the most accurate findings 

1. Added Value 

• Personalized cohort comparison increased detection by 11% 
• Helps detect overexpressed targets even in wild-type (non-mutated) tumors (e.g., KIT in GIST) 

🧬 Implications for Practice 

• RNA-Seq expression analysis offers added clinical value where DNA panels fail 
• Early integration is crucial; several patients declined too quickly to benefit 
• Use of dynamic, patient-specific comparator cohorts avoids misinterpretation 
• Manual curation still plays a key role in clinical decision-making 

🩺 Limitations & Next Steps 

• Small cohort with diverse tumor types 
• Need for broader clinical validation 
• Highlights urgency for shared pediatric datasets and tools like the NCI Childhood Cancer Data Initiative (CCDI) 

🧠 Takeaway 

CARE RNA analysis can guide precision oncology for pediatric and AYA (adolescent and young adult) patients where standard tests fall short. The future of pediatric oncology lies in integrated, multi-omic, and context-aware diagnostics. 

🔗 Full article: npj Precision Oncology (2025)