title: Germline mutations in the PAF1 complex gene CTR9 predispose to Wilms tumour.
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.
authors.affiliation: 1] Division of Genetics and Epidemiology, Institute of Cancer Research, London SM2 5NG, UK [2].
authors.forename: Sandra
authors.initials: S
authors.lastname: Hanks
authors.affiliation: 1] Division of Genetics and Epidemiology, Institute of Cancer Research, London SM2 5NG, UK [2].
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Perdeaux
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London SM2 5NG, UK.
authors.forename: Sheila
authors.initials: S
authors.lastname: Seal
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London SM2 5NG, UK.
authors.forename: Elise
authors.initials: E
authors.lastname: Ruark
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London SM2 5NG, UK.
authors.forename: Shazia S
authors.initials: SS
authors.lastname: Mahamdallie
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London SM2 5NG, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Murray
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London SM2 5NG, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Ramsay
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London SM2 5NG, UK.
authors.forename: Silvana
authors.initials: S
authors.lastname: Del Vecchio Duarte
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London SM2 5NG, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Zachariou
authors.affiliation: 1] Division of Genetics and Epidemiology, Institute of Cancer Research, London SM2 5NG, UK [2] Cancer Genetics Unit, Royal Marsden Hospital NHS Foundation Trust, London SM2 5PT, UK.
authors.forename: Bianca
authors.initials: B
authors.lastname: de Souza
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London SM2 5NG, UK.
authors.forename: Margaret
authors.initials: M
authors.lastname: Warren-Perry
authors.affiliation: Division of Genetics and Epidemiology, Institute of Cancer Research, London SM2 5NG, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Elliott
authors.affiliation: Department of Paediatric Haematology-Oncology, Red Cross Children's Hospital, University of Cape Town, Cape Town 7700, South Africa.
authors.forename: Alan
authors.initials: A
authors.lastname: Davidson
authors.affiliation: Department of Paediatrics, Great Western Hospital, Swindon SN3 6BB, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Price
authors.affiliation: Childhood Cancer Research Group, University of Oxford, Oxford OX1 2JD, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: Stiller
authors.affiliation: Molecular Haematology and Cancer Biology Unit, Institute of Child Health, University College London, London WC1E 6BT, UK.
authors.forename: Kathy
authors.initials: K
authors.lastname: Pritchard-Jones
authors.affiliation: 1] Division of Genetics and Epidemiology, Institute of Cancer Research, London SM2 5NG, UK [2] Cancer Genetics Unit, Royal Marsden Hospital NHS Foundation Trust, London SM2 5PT, UK.
authors.forename: Nazneen
authors.initials: N
authors.lastname: Rahman
mesh_terms: D017398:Alternative Splicing; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D059472:Exome; D005091:Exons; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007668:Kidney / Q000473:pathology; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D010750:Phosphoproteins / Q000235:genetics*; D014157:Transcription Factors; D009396:Wilms Tumor / Q000235:genetics*
chemical_list: C484387:CTR9 protein, human; D009687:Nuclear Proteins; C501972:PAF1 protein, human; D010750:Phosphoproteins; D014157:Transcription Factors
references.citation: Nature. 2013 Jan 17;493(7432):406-10
references.pmid: 23242139
references.citation: EMBO Rep. 2007 Sep;8(9):858-63
references.pmid: 17721442
references.citation: Br J Cancer. 2000 Jul;83(2):177-83
references.pmid: 10901367
references.citation: Nat Genet. 2014 Aug;46(8):912-918
references.pmid: 25017105
references.citation: Cell Stem Cell. 2009 May 8;4(5):403-15
references.pmid: 19345177
references.citation: Nat Genet. 1996 Aug;13(4):461-3
references.pmid: 8696342
references.citation: Nat Genet. 2002 Dec;32(4):676-80
references.pmid: 12434154
references.citation: Cell Stress Chaperones. 2011 Jul;16(4):353-67
references.pmid: 21153002
references.citation: Biochim Biophys Acta. 2013 Jan;1829(1):116-26
references.pmid: 22982193
references.citation: Biochim Biophys Acta. 2010 May-Jun;1799(5-6):379-88
references.pmid: 20060942
references.citation: Mol Cell Biol. 2002 Apr;22(7):1971-80
references.pmid: 11884586
references.citation: J Med Genet. 2006 Sep;43(9):705-15
references.pmid: 16690728
references.citation: Genome Res. 2011 Jun;21(6):936-9
references.pmid: 20980556
references.citation: Ann Oncol. 2012 Sep;23(9):2457-2463
references.pmid: 22415585
references.citation: Cancer Res. 1998 Apr 1;58(7):1387-90
references.pmid: 9537236