Germline mutations in the PAF1 complex gene CTR9 predispose to Wilms tumour.
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Date
2014-08-07Author
Hanks, S
Perdeaux, ER
Seal, S
Ruark, E
Mahamdallie, SS
Murray, A
Ramsay, E
Del Vecchio Duarte, S
Zachariou, A
de Souza, B
Warren-Perry, M
Elliott, A
Davidson, A
Price, H
Stiller, C
Pritchard-Jones, K
Rahman, N
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Subject
Kidney
Lymphocytes
Humans
Genetic Predisposition to Disease
Nuclear Proteins
Phosphoproteins
Transcription Factors
Pedigree
DNA Mutational Analysis
Alternative Splicing
Heterozygote
Germ-Line Mutation
Exons
Child, Preschool
Infant
Family Health
Female
Male
Wilms Tumor
Exome
Research team
Medicine Drug Development Unit (de Bono)
Genetic Susceptibility
Language
eng
Date accepted
2014-06-13
License start date
2014-08-07
Citation
Nature communications, 2014, 5 pp. 4398 - ?
Publisher
NATURE PUBLISHING GROUP