title: A review on the molecular diagnostics of Lynch syndrome: a central role for the pathology laboratory.
abstract: Lynch syndrome (LS) is caused by mutations in mismatch repair genes and is characterized by a high cumulative risk for the development of mainly colorectal carcinoma and endometrial carcinoma. Early detection of LS is important since surveillance can reduce morbidity and mortality. However, the diagnosis of LS is complicated by the absence of a pre-morbid phenotype and germline mutation analysis is expensive and time consuming. Therefore it is standard practice to precede germline mutation analysis by a molecular diagnostic work-up of tumours, guided by clinical and pathological criteria, to select patients for germline mutation analysis. In this review we address these molecular analyses, the central role for the pathologist in the selection of patients for germline diagnostics of LS, as well as the molecular basis of LS.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
authors.forename: Margot G F
authors.initials: MG
authors.lastname: van Lier
authors.forename: Anja
authors.initials: A
authors.lastname: Wagner
authors.forename: Monique E
authors.initials: ME
authors.lastname: van Leerdam
authors.forename: Katharina
authors.initials: K
authors.lastname: Biermann
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Kuipers
authors.forename: Ewout W
authors.initials: EW
authors.lastname: Steyerberg
authors.forename: Hendrikus Jan
authors.initials: HJ
authors.lastname: Dubbink
authors.forename: Winand N M
authors.initials: WN
authors.lastname: Dinjens
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D053843:DNA Mismatch Repair / Q000235:genetics*; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D057089:Pathology, Molecular; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012307:Risk Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein