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

Sandra Hanks; Elizabeth R. Perdeaux; Sheila Seal; Elise Ruark; Shazia S. Mahamdallie; Anne Murray; Emma Ramsay; Silvana Del Vecchio Duarte; Anna Zachariou; Bianca De Souza; Margaret Warren-Perry; Anna Elliott; Alan Davidson; Helen Price; Charles Stiller; Kathy Pritchard-Jones; Nazneen Rahman

doi:10.1038/ncomms5398

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

Sandra Hanks
, Elizabeth R. Perdeaux
, Sheila Seal
, Elise Ruark
, Shazia S. Mahamdallie
, Anne Murray
, Emma Ramsay
, Silvana Del Vecchio Duarte
, Anna Zachariou
, Bianca De Souza
, Margaret Warren-Perry
, Anna Elliott
, Alan Davidson
, Helen Price
, Charles Stiller
, Kathy Pritchard-Jones
, Nazneen Rahman^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

87 Citations (Scopus)

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.

Original language	English
Article number	4398
Journal	Nature Communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms5398
Publication status	Published - 7 Aug 2014
Externally published	Yes

Bibliographical note

Funding Information:
We thank the families for their participation in our research and the physicians and nurses that recruited them. Samples were collected through the Factors Associated with Childhood Tumours (FACT) study, which is a Children’s Cancer and Leukaemia Group (CCLG) Study (the UK National Research Ethics Service Reference: 05/MRE02/17). We are grateful to Darshna Dudakia, Jessie Bull, Rosy Williams, Usha Kini and Judith Kingston for assistance in recruitment. The CCLG receives funding from the UK Department of Health, the National Cancer Intelligence Network, the Scottish Government and Children with Cancer UK. We acknowledge use of services provided by the Institute of Cancer Research Genetics Core Facility, which is managed by Sandra Hanks and Nazneen Rahman. We acknowledge NHS funding to the Royal Marsden/ICR NIHR Biomedical Research Centre. This research was supported by the Wellcome Trust (088804/Z/09/Z), Cancer Research UK (C8620_A9024) and the Institute of Cancer Research, UK.

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10.1038/ncomms5398

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Hanks, S., Perdeaux, E. R., Seal, S., Ruark, E., Mahamdallie, S. S., 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. (2014). Germline mutations in the PAF1 complex gene CTR9 predispose to Wilms tumour. Nature Communications, 5, Article 4398. https://doi.org/10.1038/ncomms5398

@article{d985823d387b4e0abfb486a06570ee40,

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.",

author = "Sandra Hanks and Perdeaux, \{Elizabeth R.\} and Sheila Seal and Elise Ruark and Mahamdallie, \{Shazia S.\} and Anne Murray and Emma Ramsay and \{Del Vecchio Duarte\}, Silvana and Anna Zachariou and \{De Souza\}, Bianca and Margaret Warren-Perry and Anna Elliott and Alan Davidson and Helen Price and Charles Stiller and Kathy Pritchard-Jones and Nazneen Rahman",

note = "Funding Information: We thank the families for their participation in our research and the physicians and nurses that recruited them. Samples were collected through the Factors Associated with Childhood Tumours (FACT) study, which is a Children{\textquoteright}s Cancer and Leukaemia Group (CCLG) Study (the UK National Research Ethics Service Reference: 05/MRE02/17). We are grateful to Darshna Dudakia, Jessie Bull, Rosy Williams, Usha Kini and Judith Kingston for assistance in recruitment. The CCLG receives funding from the UK Department of Health, the National Cancer Intelligence Network, the Scottish Government and Children with Cancer UK. We acknowledge use of services provided by the Institute of Cancer Research Genetics Core Facility, which is managed by Sandra Hanks and Nazneen Rahman. We acknowledge NHS funding to the Royal Marsden/ICR NIHR Biomedical Research Centre. This research was supported by the Wellcome Trust (088804/Z/09/Z), Cancer Research UK (C8620\_A9024) and the Institute of Cancer Research, UK.",

year = "2014",

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day = "7",

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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 2014, 'Germline mutations in the PAF1 complex gene CTR9 predispose to Wilms tumour', Nature Communications, vol. 5, 4398. https://doi.org/10.1038/ncomms5398

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T1 - Germline mutations in the PAF1 complex gene CTR9 predispose to Wilms tumour

AU - Hanks, Sandra

AU - Perdeaux, Elizabeth R.

AU - Seal, Sheila

AU - Ruark, Elise

AU - Mahamdallie, Shazia S.

AU - Murray, Anne

AU - Ramsay, Emma

AU - Del Vecchio Duarte, Silvana

AU - Zachariou, Anna

AU - De Souza, Bianca

AU - Warren-Perry, Margaret

AU - Elliott, Anna

AU - Davidson, Alan

AU - Price, Helen

AU - Stiller, Charles

AU - Pritchard-Jones, Kathy

AU - Rahman, Nazneen

N1 - Funding Information: We thank the families for their participation in our research and the physicians and nurses that recruited them. Samples were collected through the Factors Associated with Childhood Tumours (FACT) study, which is a Children’s Cancer and Leukaemia Group (CCLG) Study (the UK National Research Ethics Service Reference: 05/MRE02/17). We are grateful to Darshna Dudakia, Jessie Bull, Rosy Williams, Usha Kini and Judith Kingston for assistance in recruitment. The CCLG receives funding from the UK Department of Health, the National Cancer Intelligence Network, the Scottish Government and Children with Cancer UK. We acknowledge use of services provided by the Institute of Cancer Research Genetics Core Facility, which is managed by Sandra Hanks and Nazneen Rahman. We acknowledge NHS funding to the Royal Marsden/ICR NIHR Biomedical Research Centre. This research was supported by the Wellcome Trust (088804/Z/09/Z), Cancer Research UK (C8620_A9024) and the Institute of Cancer Research, UK.

PY - 2014/8/7

Y1 - 2014/8/7

N2 - 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.

AB - 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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U2 - 10.1038/ncomms5398

DO - 10.1038/ncomms5398

M3 - Article

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AN - SCOPUS:84907342992

SN - 2041-1723

VL - 5

JO - Nature Communications

JF - Nature Communications

M1 - 4398

ER -

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

Abstract

Bibliographical note

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