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

✍ Scribed by Hanks, Sandra; Perdeaux, Elizabeth R.; Seal, Sheila; Ruark, Elise; Mahamdallie, Shazia S.; Murray, Anne; Ramsay, Emma; Del Vecchio Duarte, Silvana; Zachariou, Anna; de Souza, Bianca; Warren-Perry, Margaret; Elliott, Anna; Davidson, Alan; Price, Helen; Stiller, Charles; Pritchard-Jones, Kathy; Rahman, Nazneen

• Book ID: 125828764
• Publisher: Nature Publishing Group
• Year: 2014
• Tongue: English
• Weight: 495 KB
• Volume: 5
• Category: Article
• ISSN: 2041-1723
• DOI: 10.1038/ncomms5398

✦ Synopsis

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.