title: Germline mutation of RPS20, encoding a ribosomal protein, causes predisposition to hereditary nonpolyposis colorectal carcinoma without DNA mismatch repair deficiency.
abstract: Little is known about the genetic factors that contribute to familial colorectal cancer type X (FCCX), characterized by hereditary nonpolyposis colorectal carcinoma with no mismatch repair defects. Genetic linkage analysis, exome sequencing, tumor studies, and functional investigations of 4 generations of a FCCX family led to the identification of a truncating germline mutation in RPS20, which encodes a component (S20) of the small ribosomal subunit and is a new colon cancer predisposition gene. The mutation was associated with a defect in pre-ribosomal RNA maturation. Our findings show that mutations in a gene encoding a ribosomal protein can predispose individuals to microsatellite-stable colon cancer. Evaluation of additional FCCX families for mutations in RPS20 and other ribosome-associated genes is warranted.
authors.affiliation: Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland. Electronic address: Taina.Nieminen@Helsinki.Fi.
authors.forename: Taina T
authors.initials: TT
authors.lastname: Nieminen
authors.affiliation: Laboratoire de Biologie Moleculaire Eucaryote, UPS, Université de Toulouse, Toulouse, France; Centre National de la Recherche Scientifique, UMR 5099, Toulouse, France.
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: O'Donohue
authors.affiliation: Human Cancer Genetics Program, Ohio State University, Columbus, Ohio; Department of Specialty Medicine, OU-HCOM, Athens, Ohio.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Research Programs Unit, Molecular Neurology, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland; Folkhälsan Institute of Genetics, Helsinki, Finland.
authors.forename: Hannes
authors.initials: H
authors.lastname: Lohi
authors.affiliation: The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada; McLaughlin Centre and Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
authors.affiliation: The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Paterson
authors.affiliation: Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Ellonen
authors.affiliation: Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland; Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
authors.forename: Wael M
authors.initials: WM
authors.lastname: Abdel-Rahman
authors.affiliation: Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland; Department of Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Valo
authors.affiliation: Department of Surgery, Jyväskylä Central Hospital, Jyväskylä, Finland; Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jukka-Pekka
authors.initials: JP
authors.lastname: Mecklin
authors.affiliation: Second Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Heikki J
authors.initials: HJ
authors.lastname: Järvinen
authors.affiliation: Laboratoire de Biologie Moleculaire Eucaryote, UPS, Université de Toulouse, Toulouse, France; Centre National de la Recherche Scientifique, UMR 5099, Toulouse, France.
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Gleizes
authors.affiliation: Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Peltomäki
mesh_terms: D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D053843:DNA Mismatch Repair; D004252:DNA Mutational Analysis; D055354:Exosomes; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D018095:Germ-Line Mutation; D040941:Heredity; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D012269:Ribosomal Proteins / Q000235:genetics*; D012307:Risk Factors
chemical_list: D012269:Ribosomal Proteins; C029611:ribosomal protein S20
keywords: Colon Cancer; Exome Sequencing; Hereditary Nonpolyposis Colorectal Cancer; Ribosome