Germline mutations in the PAF1 complex gene CTR9 predispose to Wilms tumour

Nat Commun. 2014 Aug 7;5:4398. doi: 10.1038/ncomms5398.


Wilms tumour is a childhood kidney cancer. Here we identify inactivating CTR9 mutations in 3 of 35 Wilms tumour families, through exome and Sanger sequencing. By contrast, no similar mutations are present in 1,000 population controls (P<0.0001). Each mutation segregates with Wilms tumour in the family and a second mutational event is present in available tumours. CTR9 is a key component of the polymerase-associated factor 1 complex which has multiple roles in RNA polymerase II regulation and is implicated in embryonic organogenesis and maintenance of embryonic stem cell pluripotency. These data establish CTR9 as a Wilms tumour predisposition gene and suggest it acts as a tumour suppressor gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Child, Preschool
  • DNA Mutational Analysis
  • Exome
  • Exons
  • Family Health
  • Female
  • Genetic Predisposition to Disease*
  • Germ-Line Mutation*
  • Heterozygote
  • Humans
  • Infant
  • Kidney / pathology
  • Lymphocytes / cytology
  • Lymphocytes / metabolism
  • Male
  • Nuclear Proteins / genetics*
  • Pedigree
  • Phosphoproteins / genetics*
  • Transcription Factors
  • Wilms Tumor / genetics*


  • CTR9 protein, human
  • Nuclear Proteins
  • PAF1 protein, human
  • Phosphoproteins
  • Transcription Factors