Detection analysis of microsatellite instability status for the diagnosis and therapy of Lynch syndrome-related cancers

Lynch syndrome (LS) is an autosomal dominant genetic disorder that is characterized by an increased risk of developing colorectal cancer. LS is associated with germline mutations in DNA mismatch repair genes (MMR) that are involved in the correction of nucleotide misalignments that may arise during DNA replication. The deficiency of the MMR complex results in a high rate of mutations in repetitive DNA sequences known as microsatellites; these, because of their structure, are more prone to errors during replication. This condition is known as microsatellite instability (MSI) and is present in about 95% of the tumors associated with LS. MSI analysis is used for making clinical diagnosis of LS. All the individuals showing MSI-high status on the tumor tissue should undergo to genetic testing to identify pathogenetic mutation in one of the MMR genes. The identification of the mutation allows making an early diagnosis, in individuals belonging to families at risk. Moreover, the MSI testing in addition to the key role in the molecular diagnosis of LS, has also a very important role in identifying the most appropriate therapeutic approach for LS patients. Recently, novel therapeutic approaches such as immunotherapy, which represent a viable alternative to traditional therapeutic methods, give a good life expectancy to patients showing a MSI-high status, who have already developed a LS-related cancer. In this paper, through a review of the most recent literature, we present this dual role of MSI analysis in Lynch syndrome.