Germline mutation of RPS20, encoding a ribosomal protein, causes predisposition to hereditary nonpolyposis colorectal carcinoma without DNA mismatch repair deficiency

Taina T Nieminen; Marie-Françoise O'Donohue; Yunpeng Wu; Hannes Lohi; Stephen W Scherer; Andrew D Paterson; Pekka Ellonen; Wael M Abdel-Rahman; Satu Valo; Jukka-Pekka Mecklin; Heikki J Järvinen; Pierre-Emmanuel Gleizes; Päivi Peltomäki

doi:10.1053/j.gastro.2014.06.009

Germline mutation of RPS20, encoding a ribosomal protein, causes predisposition to hereditary nonpolyposis colorectal carcinoma without DNA mismatch repair deficiency

Gastroenterology. 2014 Sep;147(3):595-598.e5. doi: 10.1053/j.gastro.2014.06.009. Epub 2014 Jun 15.

Affiliations

¹ Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland. Electronic address: Taina.Nieminen@Helsinki.Fi.
² Laboratoire de Biologie Moleculaire Eucaryote, UPS, Université de Toulouse, Toulouse, France; Centre National de la Recherche Scientifique, UMR 5099, Toulouse, France.
³ Human Cancer Genetics Program, Ohio State University, Columbus, Ohio; Department of Specialty Medicine, OU-HCOM, Athens, Ohio.
⁴ 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.
⁵ 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.
⁶ The Centre for Applied Genomics and Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
⁷ Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
⁸ 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.
⁹ Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland; Department of Biosciences, University of Helsinki, Helsinki, Finland.
¹⁰ Department of Surgery, Jyväskylä Central Hospital, Jyväskylä, Finland; Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
¹¹ Second Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland.
¹² Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland.

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.

Keywords: Colon Cancer; Exome Sequencing; Hereditary Nonpolyposis Colorectal Cancer; Ribosome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
DNA Mismatch Repair*
DNA Mutational Analysis
Exosomes
Female
Genetic Linkage
Genetic Predisposition to Disease
Genetic Testing / methods
Germ-Line Mutation*
Heredity
Humans
Male
Middle Aged
Pedigree
Phenotype
Ribosomal Proteins / genetics*
Risk Factors

Substances

Ribosomal Proteins
ribosomal protein S20