Evaluation of microsatellite instability (MSI) status in 11,573 diverse solid tumors using comprehensive genomic profiling (CGP)

1523Background: MSI status is predictive of anti-PD-1/L1 therapy efficacy independent of tumor histology. This study describes the development and validation of a novel computational method to assess MSI status. In addition, we sought to determine the MSI prevalence and mutation characteristics in the cohort by applying the method to 11,573 clinical solid tumor cases previously assayed with CGP. Methods: To determine MSI status, 114 intronic homopolymer repeat loci with adequate coverage on the CGP panel were analyzed for length variability and compiled into an overall MSI score via principal components analysis. Translation of the MSI score to MSI-H (microsatellite high) or MSS (microsatellite stable) was established using training data. A matched-normal sample is not required, and CGP is accurate when tumor content is at least 20%. Results: Our methodology was validated in 69 samples with MSI status (20 MSI-H, 49 MSS) previously determined by standard clinical testing (PCR or immunohistochemistry). Conc...