Trupti N Patel

Microsatellite instability across various tumor types: diagnostic criteria, methods of detection and bio-clinical associations

Microsatellite instability (MSI) is a specific molecular tumor phenotype recognized by accumulation of mutations in microsatellites. Microsatellites are repetitive DNA sequences consisting of 1-6 nucleotides. MSI is caused by defective DNA mismatch repair, resulting from hereditary or somatic mutations in the MLH1, MSH2, MSH6, PMS2 genes or hypermethylation of the MLH1 promoter. MSI is most often observed in the uterine cancer (≈ 30%), gastric cancer (≈ 20%), colon cancer (≈ 15%) and rectal carcinomas (≈ 6%) and is much less common in other tumor types. MSI testing has become particularly relevant after the establishment of the predictive role of MSI for the efficacy of immune checkpoint inhibitors, one of the most promising and widely used therapeutic agents in oncology today.