New publication in Gastroenterology

Germline mutation of RPS20, a ribosomal protein gene, predisposes 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, and Päivi Peltomäki

The predisposing genes for FCCX, hereditary nonpolyposis colorectal carcinoma with no mismatch repair defects, are largely unknown. Genetic linkage analysis, exome sequencing, tumor studies, and functional investigations of a four-generation FCCX family resulted in the identification of a truncating germline mutation in RPS20, a novel colon cancer predisposition gene encoding a component (S20) of the small ribosomal subunit. The mutation was associated with a defect in pre-rRNA maturation. Our findings show that a mutant ribosomal protein gene can underlie hereditary predisposition to microsatellite-stable colon cancer. Evaluation of additional FCCX families for mutations in RPS20 and other ribosome-associated genes is warranted.

Gastroenterology, 2014.