Microsatellite Instability (MSI) is a condition that appears on the DNA of specific cells (ex cancer cells), where the number of microsatellites (short repeats of DNA sequences) in these cells, is different from the repeats that exist in the normal cells of the same individual. This instability is caused due to malfunction of the repair mechanism (Mismatch Repair Mechanism, MMR) of damages on the DNA that occur during DNA replication.
The presence of Microsatellite Instability (MSI High, MSI-H) is found in 90% of cases of tumors arising in patients with hereditary Lynch syndrome and in 10%-15% of the sporadic colorectal cancers. Sporadic MSI-H tumors can be distinguished from the hereditary ones through somatic mutation analysis of the BRAF gene or loss of MLH1 expression. Somatic mutations in the BRAF gene occur only in sporadic MSI-H tumors but not in Lynch-associated CRC (Colorectal Cancers). Similarly, MLH1 promoter methylation rarely occurs in Lynch syndrome-associated cancers, while is common in sporadic MSI-High cancers.
The knowledge of the MSI status is valuable for: