Lynch syndrome is the most common inherited cancer syndrome affecting 1:280 individuals. Lynch syndrome carriers have 30-80% lifetime risk of developing malignancies, most commonly affecting patients’ bowel (colorectal cancer, CRC) and in female patients the uterus (endometrial cancer, EC).
Lynch syndrome is inherited via a germline alteration in one of the so-called DNA Mismatch Repair (MMR) genes. Due to the lack of MMR function, mistakes during DNA replication remain uncorrected leading to accumulation of high numbers of mutations, particularly at repetitive gene sequences (micorsatellites). These mutations have two relevant consequences: first, the mutations can inactivate genes responsible for controlling cell growth and devision, thus initiating tumor growth; second, these mutations give rise to altered proteins, which can be recognized by the immune system. Tumors displaying MMR deficiency are called MMR-deficient and the resulting genomic instability type is termed microsatellite instability (MSI).