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

Hanks, Sandra; Perdeaux, Elizabeth R; Seal, Sheila; Ruark, Elise; Mahamdallie, Shazia S; Murray, Anne; Ramsay, Emma; Del Vecchio Duarte, Silvana et al. · Nat Commun · 2014

case_control · Level III

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Abstract

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.

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