Germline Mutation of RPS20, Encoding a Ribosomal Protein, Causes Predisposition to Hereditary Nonpolyposis Colorectal Carcinoma Without DNA Mismatch Repair Deficiency

Overview

Journal Gastroenterology

Specialty Gastroenterology

Date 2014 Jun 19

PMID 24941021

Citations 86

Authors

Taina T Nieminen

Marie-Francoise ODonohue

Yunpeng Wu

Hannes Lohi

Stephen W Scherer

Andrew D Paterson

Pekka Ellonen

Wael M Abdel-Rahman

Satu Valo

Jukka-Pekka Mecklin

Heikki J Jarvinen

Pierre-Emmanuel Gleizes

Paivi Peltomaki

Affiliations

Soon will be listed here.

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.

Citing Articles

New RPS20 gene variant in colorectal cancer diagnosis: insight from a large series of patients.

Amiot J, Gubeljak L, Fontaine A, Smith D, Mortemousque I, Parodi N Fam Cancer. 2025; 24(1):22.

PMID: 39920491 DOI: 10.1007/s10689-025-00446-y.

Genetics, diet, microbiota, and metabolome: partners in crime for colon carcinogenesis.

La Vecchia M, Sala G, Sculco M, Aspesi A, Dianzani I Clin Exp Med. 2024; 24(1):248.

PMID: 39470880 PMC: 11522171. DOI: 10.1007/s10238-024-01505-x.

Clinical significance of ribosomal protein S15 expression in patients with colorectal cancer liver metastases.

Sakano Y, Matoba D, Noda T, Kobayashi S, Yamada D, Tomimaru Y J Hepatobiliary Pancreat Sci. 2024; 31(9):611-624.

PMID: 38838053 PMC: 11503462. DOI: 10.1002/jhbp.12012.

Germline NPAT inactivating variants as cause of hereditary colorectal cancer.

Terradas M, Schubert S, Viana-Errasti J, Ruano D, Aiza G, Nielsen M Eur J Hum Genet. 2024; 32(7):871-875.

PMID: 38778081 PMC: 11219789. DOI: 10.1038/s41431-024-01625-8.

Potentials of ribosomopathy gene as pharmaceutical targets for cancer treatment.

Wang M, Vulcano S, Xu C, Xie R, Peng W, Wang J J Pharm Anal. 2024; 14(3):308-320.

PMID: 38618250 PMC: 11010632. DOI: 10.1016/j.jpha.2023.10.001.

References

Nieminen T, Abdel-Rahman W, Ristimaki A, Lappalainen M, Lahermo P, Mecklin J . BMPR1A mutations in hereditary nonpolyposis colorectal cancer without mismatch repair deficiency. Gastroenterology. 2011; 141(1):e23-6. DOI: 10.1053/j.gastro.2011.03.063. View

Chomczynski P . A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. Biotechniques. 1993; 15(3):532-4, 536-7. View

Gazda H, Preti M, Sheen M, ODonohue M, Vlachos A, Davies S . Frameshift mutation in p53 regulator RPL26 is associated with multiple physical abnormalities and a specific pre-ribosomal RNA processing defect in diamond-blackfan anemia. Hum Mutat. 2012; 33(7):1037-44. PMC: 3370062. DOI: 10.1002/humu.22081. View

Huang J, Kuismanen S, Liu T, Chadwick R, Johnson C, Stevens M . MSH6 and MSH3 are rarely involved in genetic predisposition to nonpolypotic colon cancer. Cancer Res. 2001; 61(4):1619-23. View

Pannicke U, Baumann B, Fuchs S, Henneke P, Rensing-Ehl A, Rizzi M . Deficiency of innate and acquired immunity caused by an IKBKB mutation. N Engl J Med. 2013; 369(26):2504-14. DOI: 10.1056/NEJMoa1309199. View

Landowski M, ODonohue M, Buros C, Ghazvinian R, Montel-Lehry N, Vlachos A . Novel deletion of RPL15 identified by array-comparative genomic hybridization in Diamond-Blackfan anemia. Hum Genet. 2013; 132(11):1265-74. PMC: 3797874. DOI: 10.1007/s00439-013-1326-z. View

Sjoblom T, Jones S, Wood L, Parsons D, Lin J, Barber T . The consensus coding sequences of human breast and colorectal cancers. Science. 2006; 314(5797):268-74. DOI: 10.1126/science.1133427. View

Umar A, Boland C, Terdiman J, Syngal S, de la Chapelle A, Ruschoff J . Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst. 2004; 96(4):261-8. PMC: 2933058. DOI: 10.1093/jnci/djh034. View

Amsterdam A, Sadler K, Lai K, Farrington S, Bronson R, Lees J . Many ribosomal protein genes are cancer genes in zebrafish. PLoS Biol. 2004; 2(5):E139. PMC: 406397. DOI: 10.1371/journal.pbio.0020139. View

10.

Thompson B, Spurdle A, Plazzer J, Greenblatt M, Akagi K, Al-Mulla F . Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database. Nat Genet. 2013; 46(2):107-115. PMC: 4294709. DOI: 10.1038/ng.2854. View

11.

Ye K, Schulz M, Long Q, Apweiler R, Ning Z . Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads. Bioinformatics. 2009; 25(21):2865-71. PMC: 2781750. DOI: 10.1093/bioinformatics/btp394. View

12.

. Comprehensive molecular characterization of human colon and rectal cancer. Nature. 2012; 487(7407):330-7. PMC: 3401966. DOI: 10.1038/nature11252. View

13.

Vasen H, Watson P, Mecklin J, Lynch H . New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology. 1999; 116(6):1453-6. DOI: 10.1016/s0016-5085(99)70510-x. View

14.

Peltomaki P, Aaltonen L, Sistonen P, Pylkkanen L, Mecklin J, Jarvinen H . Genetic mapping of a locus predisposing to human colorectal cancer. Science. 1993; 260(5109):810-2. DOI: 10.1126/science.8484120. View

15.

Kuismanen S, Holmberg M, Salovaara R, de la Chapelle A, Peltomaki P . Genetic and epigenetic modification of MLH1 accounts for a major share of microsatellite-unstable colorectal cancers. Am J Pathol. 2000; 156(5):1773-9. PMC: 1876911. DOI: 10.1016/S0002-9440(10)65048-1. View

16.

Lindor N . Familial colorectal cancer type X: the other half of hereditary nonpolyposis colon cancer syndrome. Surg Oncol Clin N Am. 2009; 18(4):637-45. PMC: 3454516. DOI: 10.1016/j.soc.2009.07.003. View

17.

Vasen H, Mecklin J, Khan P, Lynch H . The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum. 1991; 34(5):424-5. DOI: 10.1007/BF02053699. View

18.

McGowan K, Li J, Park C, Beaudry V, Tabor H, Sabnis A . Ribosomal mutations cause p53-mediated dark skin and pleiotropic effects. Nat Genet. 2008; 40(8):963-70. PMC: 3979291. DOI: 10.1038/ng.188. View

19.

Renkonen E, Zhang Y, Lohi H, Salovaara R, Abdel-Rahman W, Nilbert M . Altered expression of MLH1, MSH2, and MSH6 in predisposition to hereditary nonpolyposis colorectal cancer. J Clin Oncol. 2003; 21(19):3629-37. DOI: 10.1200/JCO.2003.03.181. View

20.

Daftuar L, Zhu Y, Jacq X, Prives C . Ribosomal proteins RPL37, RPS15 and RPS20 regulate the Mdm2-p53-MdmX network. PLoS One. 2013; 8(7):e68667. PMC: 3713000. DOI: 10.1371/journal.pone.0068667. View