title: Lynch or not Lynch? Is that always a question?
abstract: The familial cancer syndrome referred to as Lynch I and II was renamed hereditary nonpolyposis colorectal cancer (HNPCC) only to revert later to Lynch syndrome (LS). LS is the most frequent human predisposition for the development of colorectal cancer (CRC), and probably also for endometrial and gastric cancers, although it has yet to acquire a consensus name. Its estimated prevalence ranges widely from 2% to 7% of all CRCs due to the fact that tumors from patients with LS are difficult to recognize at both the clinical and molecular level. This review is based on two assumptions. First, all LS patients inherit a predisposition to develop CRC (without polyposis) and/or other tumors from the Lynch spectrum. Second, all LS patients have a germline defect in one of the DNA mismatch repair (MMR) genes. When a somatic second hit inactivates the relevant MMR gene, the consequence is instability of DNA repeat sequences such as microsatellites and the tumors are referred to as having the microsatellite instability (MSI) phenotype. However, some of the inherited predisposition to develop CRC without concurrent polyposis, termed HNPCC, is found in non-LS patients, while not all MSI tumors are from LS cases. LS tumors are therefore at the junction of inherited and MSI cases. We describe here the defining characteristics of LS tumors that differentiate them from inherited non-MSI tumors and from non-inherited MSI tumors.
authors.affiliation: INSERM, UMRS 938, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancers, Paris, France.
authors.forename: Chrystelle
authors.initials: C
authors.lastname: Colas
authors.forename: Florence
authors.initials: F
authors.lastname: Coulet
authors.forename: Magali
authors.initials: M
authors.lastname: Svrcek
authors.forename: Ada
authors.initials: A
authors.lastname: Collura
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Fléjou
authors.forename: Alex
authors.initials: A
authors.lastname: Duval
authors.forename: Richard
authors.initials: R
authors.lastname: Hamelin
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000473:pathology*; D053843:DNA Mismatch Repair / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D053842:Microsatellite Instability; D018895:Microsatellite Repeats / Q000235:genetics*