Previously, published evidence of the value of RNA sequencing has been limited by studies with small sample sizes and enriched cohorts. This study by Ambry is the largest to examine the impact of paired DNA and RNA analysis in hereditary cancer testing.

In the study, tests from 43,524 patients who underwent paired DNA-RNA genetic testing using Ambry’s +RNAinsight from March 2019 through April 2020 were examined to determine if the paired sequencing detected more pathogenic variants than DNA testing alone. The analysis identified patients who had disease-causing alterations that DNA testing alone would have misinterpreted. Examining the RNA data resolved variant findings in 549 patients (1 in 79 patients) by providing the required functional data for more accurate interpretation of splicing variants. In addition, the analysis showed that 1 of every 950 patients had a pathogenic deep intronic variant that would not have appeared in DNA testing alone.

The study was published in npj Genomic Medicine. Congratulations to Carrie Horton, senior clinical research specialist, and Rachid Karam, M.D., Ph.D., for leading this important study.