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

Area of Science:

• Genomics
• Oncology
• Bioinformatics

Background:

• Pediatric cancers often lack identifiable mutations, necessitating alternative genomic strategies for therapeutic target discovery.
• Identifying actionable targets in relapsed, refractory, or rare pediatric and young adult cancers remains a clinical challenge.

Purpose of the Study:

• To evaluate the utility of comparative RNA sequencing analysis for identifying therapeutic targets in pediatric and young adult cancers.
• To assess the clinical significance and implementation of findings from RNA expression analysis in a patient cohort.

Main Methods:

• RNA sequencing data from 33 pediatric and young adult cancer patients were analyzed using the Comparative Analysis of RNA Expression (CARE) pipeline.
• The CARE pipeline identified activated cancer driver pathways and nominated potential treatments.
• The study compared the CARE pipeline's performance against other gene expression outlier detection methods.

Main Results:

• The CARE analysis revealed findings of potential clinical significance in 31 out of 33 (94%) patients.
• Therapeutic strategies based on these findings were implemented in 5 patients, resulting in defined clinical benefit for 3.
• The composition of comparator cohorts significantly influenced the detection of gene expression outliers.

Conclusions:

• Comparative RNA sequencing analysis, such as the CARE approach, holds significant clinical utility for identifying therapeutic targets in pediatric and young adult cancers.
• The study highlights the practical challenges associated with implementing these genomic analyses in clinical settings.
• This approach offers a valuable alternative for cancers with a low incidence of targetable mutations.