Clinical and Analytical Validation of a Combined RNA and DNA Exome Assay

RNA sequencing (RNA-seq) can support the identification of clinically actionable findings from a single tumor sample when combined with whole exome sequencing (WES) to significantly impact clinical decision-making for cancer patients. Our study presents a comprehensive assay based on clinical guidelines for evaluating gene expression levels, genomic events and their correlations using an integrated RNA-seq and WES approach. We used a novel three-step approach of analytical validation on newly created somatic reference exomes and orthogonally tested it on patient samples. The application of this integrated assay on tumors allowed the rescue of clinical somatic variants based on RNA expression, and the identification of alterations in clinically actionable genes for patients.