Microsatellite Instability is the accumulation of insertion or deletion errors at
microsatellite repeat sequences in cancerous cells as a result of a functional deficiency
within one or more major DNA mismatch repair proteins (dMMR). Mononucleotide
(homopolymer) repeat microsatellite sequences found throughout the genome are
particularly sensitive to transcription errors. Thus, high frequency microsatellite
instability (MSI-H) is considered a marker for the presence of mutations in, or
methylation silencing of, certain major DNA MMR genes.
Historically MSI has been used to screen for Lynch Syndrome, a dominant hereditary
cancer propensity. Recently, MSI status has been rediscovered as a biomarker for
immunotherapeutic response, making MSI status an increasingly relevant tool in
genetic- and immuno-oncology.