title: A de novo MLH1 germ line mutation in a 31-year-old colorectal cancer patient.
abstract: Hereditary nonpolyposis colorectal cancer is an autosomal dominant cancer predisposition syndrome caused by inherited germ line mutations in DNA mismatch repair genes, predominantly MSH2 and MLH1. Here we report the first proven de novo germ line mutation in MLH1 (c.666dupA) identified in a 31-year-old colorectal cancer patient with the alteration being present in a heterozygous state in all three germ layers and homozygously in his colon cancer. The mutation was absent in both biological parents and all sibs available. Despite extensive polymorphic marker analysis, the parental origin of c.666dupA could not be conclusively determined, representing either a single mutational event in a parental germ cell or (maternal) gonadal mosaicism. Although rare, consequential application of the Bethesda guidelines for genetic testing should allow the clinician to readily identify colorectal cancer patients below age 50 years who carry de novo mismatch repair gene mutations.
authors.affiliation: Research Group Human Genetics, Division of Medical Genetics UKBB, Center of Biomedicine DKBW, University of Basel, Basel, Switzerland.
authors.forename: Martina
authors.initials: M
authors.lastname: Plasilova
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Roberta
authors.initials: R
authors.lastname: Okhowat
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Marra
authors.forename: Markus
authors.initials: M
authors.lastname: Mettler
authors.forename: Hansjakob
authors.initials: H
authors.lastname: Mueller
authors.forename: Karl
authors.initials: K
authors.lastname: Heinimann
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005190:Family; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1