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Article
Nature Genetics  25, 160 - 165 (2000)
doi:10.1038/76006

Identification of the familial cylindromatosis tumour-suppressor gene

Graham R. Bignell1, 23, William Warren1, 23, Sheila Seal1, Meiko Takahashi1, Elizabeth Rapley1, Rita Barfoot1, Helen Green1, Carolanne Brown1, Patrick J. Biggs1, Sunil R. Lakhani2, Christopher Jones2, Juliana Hansen3, Edward Blair4, Benedikt Hofmann5, Reiner Siebert6, Gwen Turner7, D. Gareth Evans8, Connie Schrander-Stumpel9, Frits A. Beemer10, Ans van den Ouweland11, Dicky Halley11, Bertrand Delpech12, Mark G. Cleveland13, Irene Leigh14, Jaakko Leisti15, Sonja Rasmussen16, Margaret R. Wallace16, Christiane Fenske17, Piu Banerjee17, Naoki Oiso18, Ranbir Chaggar19, Samantha Merrett19, Niamh Leonard20, Marcel Huber21, Daniel Hohl21, Pam Chapman22, John Burn22, Sally Swift1, Anna Smith1, Alan Ashworth1 & Michael R. Stratton1

1  Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, and the Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK.

2  Department of Histopathology, Royal Free & University College, Medical School, UCL, Rockefeller Building, University Street, London, UK.

3  OHSU Department of Surgery, Portland, Oregon, USA.

4  Department of Clinical Genetics, Oxford Radcliffe Hospital Trust, The Churchill, Oxford, UK.

5  Hautklinik der Medizinischen Einrichtungen, der Heinrich-Heine-Universitat, Dusseldorf, Germany.

6  Department of Human Genetics, University of Kiel, Kiel, Germany.

7  Yorkshire Regional Genetics Service, Department of Clinical Genetics, Leeds, Yorkshire, UK.

8  Regional Genetic Service, Central Manchester Healthcare NHS Trust, St Mary's Hospital, Manchester, UK.

9  Department of Clinical Genetics, Academic Hospital Maastricht, Maastricht, The Netherlands.

10  Department of Medical Genetics, University Medical Center, Utrecht, The Netherlands.

11  Department of Clinical Genetics, Erasmus Universiteit Rotterdam, Rotterdam, The Netherlands.

12  Groupe de Recherche sur l'inflammation et le Cancer UPRES EA 2122, Laboratoire d'Oncologie Moleculaire, Centre Henri-Becquerel, Rouen, France.

13  Department of Dermatology, University of Iowa, Iowa City, Iowa, USA.

14  Centre for Cutaneous Research, St Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK.

15  Department of Clinical Genetics, Oulu University Central Hospital, Kajaanintie 50, Oulu, Finland.

16  Division of Genetics, University of Florida College of Medicine, PO Box 100296, Gainesville, Florida, USA.

17  Medical Genetics Department, St George's Hospital Medical School, Tooting, London, UK.

18  Department of Dermatology, Osaka City University Medical School, 1-4-3 Asahimachi Abeno-ku, Osaka, Japan.

19  The Ludwig Institute for Cancer Research, Courtauld Building, London, UK.

20  Department of Histopathology, Royal Victoria Infirmary, Newcastle upon Tyne, UK.

21  CHUV-Service de dermatologie, Hopital Beaumont 04-421, Lausanne, Switzerland.

22  Institute for Human Genetics, University of Newcastle, Newcastle-upon-Tyne, UK.

23  These authors contributed equally to this work.

Correspondence should be addressed to Michael R. Stratton mikes@icr.ac.uk
Familial cylindromatosis is an autosomal dominant genetic predisposition to multiple tumours of the skin appendages. The susceptibility gene (CYLD) has previously been localized to chromosome 16q and has the genetic attributes of a tumour-suppressor gene (recessive oncogene). Here we have identified CYLD by detecting germline mutations in 21 cylindromatosis families and somatic mutations in 1 sporadic and 5 familial cylindromas. All mutations predict truncation or absence of the encoded protein. CYLD encodes three cytoskeletal-associated-protein−glycine-conserved (CAP−GLY) domains, which are found in proteins that coordinate the attachment of organelles to microtubules. CYLD also has sequence homology to the catalytic domain of ubiquitin carboxy-terminal hydrolases (UCH).

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Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
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