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.


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


  • Ribosomal Proteins
  • ribosomal protein S20