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

被引：76

作者：

Hanks, Sandra ^{[1
]}

Perdeaux, Elizabeth R. ^{[1
]}

Seal, Sheila ^{[1
]}

Ruark, Elise ^{[1
]}

Mahamdallie, Shazia S. ^{[1
]}

Murray, Anne ^{[1
]}

Ramsay, Emma ^{[1
]}

Duarte, Silvana Del Vecchio ^{[1
]}

Zachariou, Anna ^{[1
]}

de Souza, Bianca ^{[1
,2
]}

Warren-Perry, Margaret ^{[1
]}

Elliott, Anna ^{[1
]}

Davidson, Alan ^{[3
]}

Price, Helen ^{[4
]}

Stiller, Charles ^{[5
]}

Pritchard-Jones, Kathy ^{[6
]}

Rahman, Nazneen ^{[1
,2
]}

机构：

[1] Canc Res Inst, Div Genet & Epidemiol, London SM2 5NG, England

[2] Royal Marsden Hosp, NHS Fdn Trust, Canc Genet Unit, London SM2 5PT, England

[3] Univ Cape Town, Red Cross Childrens Hosp, Dept Paediat Haematol Oncol, ZA-7700 Cape Town, South Africa

[4] Great Western Hosp, Dept Paediat, Swindon SN3 6BB, Wilts, England

[5] Univ Oxford, Childhood Canc Res Grp, Oxford OX1 2JD, England

[6] UCL, Inst Child Hlth, Mol Haematol & Canc Biol Unit, London WC1E 6BT, England

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

基金：

英国惠康基金;

关键词：

TRANSCRIPTION; FWT1;

D O I：

10.1038/ncomms5398

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：7

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