Mismatch repair (MMR) proteins are involved in repairing errors that are formed as part of DNA replication, e.g. point mutations. Although there are several known MMR proteins, four of these play a particularly important clinical role in human cancer biology - MLH1, MSH2, MSH6 and PMS2. These four proteins are arranged as heterodimers (MLH1 complexing with PMS2 and MSH2 complexing with MSH6) to recognise mismatched nucleotide base pairs caused by errors in deletion or insertion.
A mutation in one or more of these MMR proteins leads to impaired DNA repair which can result in microsatellite instability (MSI) and increased likelihood of cancers such as colorectal and endometrial carcinomas. MMR deficiency (dMMR) caused by mutations to MMR proteins can be termed as Lynch syndrome and accounts for 3-5% and 2-3% of colorectal and endometrial carcinomas, respectively.
dMMR can be diagnosed either molecularly (through detection of MSI) or by showing loss of nuclear protein expression in tumour cells using IHC.