title: Recent discoveries in the molecular genetics of Lynch syndrome.
abstract: Lynch syndrome is the inherited predisposition to cancer caused by a germline mutation in a DNA mismatch repair gene. The consequent tumors have a characteristic microsatellite instability (MSI) phenotype. Genomic sequencing of Lynch syndrome-associated colorectal cancers (CRCs) has demonstrated that these tumors have a substantially greater number of mutations than non-MSI CRCs, and that the target mutations driving tumor behavior are also different from what occurs in sporadic tumors. There are multiple non-Lynch syndrome entities that can create clinical confusion with that disease, including the acquired methylation of MLH1, Lynch-like syndrome, and Familial CRC-Type X. Patients with Lynch syndrome-associated CRCs have a substantially better prognosis, and there is growing evidence that this is due to the generation of immunogenic frameshift peptides as a consequence of defective DNA mismatch repair, and an effective immune response to the tumor.
authors.affiliation: GI Cancer Research Laboratory, Baylor University Medical Center, Dallas, TX, 75246, USA. Rick.Boland@BSWHealth.org.|GI Cancer Research Laboratory, Baylor Scott & White Research Institute, H-250, 3500 Gaston Avenue, Dallas, TX, 75246, USA. Rick.Boland@BSWHealth.org.
authors.forename: C Richard
authors.initials: CR
authors.lastname: Boland
mesh_terms: D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D053843:DNA Mismatch Repair / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D053842:Microsatellite Instability; D000070957:MutL Protein Homolog 1 / Q000235:genetics*; D010641:Phenotype; D011379:Prognosis
chemical_list: C501486:MLH1 protein, human; D000070957:MutL Protein Homolog 1
keywords: Colorectal cancer; Genomic sequencing; Germline mutation; Hypermutated; Lynch syndrome; Lynch-like syndrome; MLH1; MSH2; Microsatellite instability; Somatic mutation