Hereditary Colorectal Cancer: State of the Art in Lynch Syndrome

SIMPLE SUMMARY: Lynch syndrome is the most common form of hereditary colorectal cancer associate to variants in Mismatch Repair (MMR) genes. Unfortunately, a large amount of variants identified in these genes remain of uncertain significance. Therefore, many individuals with a clinical suspicion of LS receive a diagnosis of Lynch-like syndrome. This review summarizes the main aspects of Lynch syndrome and recent advances in the molecular diagnosis and, in particular the main factors that determine the loss of expression of MMR genes. ABSTRACT: Hereditary non-polyposis colorectal cancer is also known as Lynch syndrome. Lynch syndrome is associated with pathogenetic variants in one of the mismatch repair (MMR) genes. In addition to colorectal cancer, the inefficiency of the MMR system leads to a greater predisposition to cancer of the endometrium and other cancers of the abdominal sphere. Molecular diagnosis is performed to identify pathogenetic variants in MMR genes. However, for many patients with clinically suspected Lynch syndrome, it is not possible to identify a pathogenic variant in MMR genes. Molecular diagnosis is essential for referring patients to specific surveillance to prevent the development of tumors related to Lynch syndrome. This review summarizes the main aspects of Lynch syndrome and recent advances in the field and, in particular, emphasizes the factors that can lead to the loss of expression of MMR genes.