Microsatellite Instability – Response to Immunotherapy

Caris Molecular Intelligence® tumor profiling includes microsatellite instability (MSI) testing via next-generation sequencing (NGS). MSI is caused by failure of the DNA mismatch repair (MMR) system. High levels of MSI correlate to an increased neoantigen burden, which may make the tumor more sensitive to immunotherapy. MSI status is reported on pages one and two of the MI Profile Report, as well as in the NGS section in the Appendix.

MSI-High Status Across Caris Molecular Intelligence Cases

Earlier studies have associated MSI-High status with benefit to immunotherapy in metastatic colorectal cancer. Recent data, however, show that MSI is a useful indicator for predicting response to pembrolizumab in any solid tumor type.1

Traditionally, MSI was measured by analyzing seven different loci by polymerase chain reaction (PCR) and comparing cancer tissue to normal tissue to identify differences in tandem repeats. To validate MSI testing via
NGS, Caris evaluated more than 7,000 loci and compared the results from PCR for 2,192 cases across 24 different tumor types (see results table). Using NGS to assess MSI status enables a more thorough analysis of the known microsatellite regions.

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Traditional Approach: normal and cancer tissue required

Caris Approach: no normal tissue required; saving resources, costs and time

 

1. D. T. Le, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. Published Online 8 June 2017. DOI: 10.1126/science.aan6733.