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

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

Author information

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

PMID:
24941021
PMCID:
PMC4155505
DOI:
10.1053/j.gastro.2014.06.009
[Indexed for MEDLINE]
Free PMC Article

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