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

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 f...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2014
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143912/
https://www.ncbi.nlm.nih.gov/pubmed/25099282
http://dx.doi.org/10.1038/ncomms5398
Descripción
Sumario: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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