Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene (original) (raw)

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Acknowledgements

We thank all the families for providing samples for this study. We are deeply indebted to German Cancer Aid for establishing the GC-HBOC and their longstanding patronage. This work was supported by grants from the German Cancer Aid (grant numbers 107054 and 107353), the Juergen-Manchot-Stiftung (L.H., H.S.), the Cancer Society Northrhine-Westphalia (D.N., E.H., H.S.), the Forschungskommission of the Heinrich-Heine-University, Düsseldorf (M.F., D.N., H.S., H. Hanenberg), the Bundesministerium für Bildung und Forschung network for Inherited Bone Marrow Failure Syndromes (H.S., H. Hanenberg) and the Deutsche Forschungsgemeinschaft SPP1230 (H. Hanenberg). We also thank N. Arnold, C. Bartram, U. Bick, W. Diestler, M. Loeffler, T. Grimm, R. Kreienberg, C. Nestle-Kraemling, B. Schlegelberger and P. Wieacker for their long-standing collaboration within the GC-HBOC. Finally, we acknowledge the excellent technical assistance of B. Kau, G. Krebsbach, J. Koehler, W. Kuss, R. Friedl and S. Engert.

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Author notes

1. Heide Hellebrand and Constanze Wiek: These authors contributed equally to the work.
2. Rita K Schmutzler and Helmut Hanenberg: These authors contributed equally to the direction of the work.

Authors and Affiliations

1. Department of Obstetrics and Gynecology, Division of Tumor Genetics, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich, Germany
   Alfons Meindl, Heide Hellebrand, Juliane Ramser & Marion Kiechle
2. Department of Pediatric Hematology, Oncology and Clinical Immunology, Children's Hospital, Heinrich-Heine-University, Düsseldorf
   Constanze Wiek, Verena Erven, Marcel Freund & Helmut Hanenberg
3. Germany,
   Constanze Wiek, Verena Erven, Marcel Freund & Helmut Hanenberg
4. Center for Familial Breast and Ovarian Cancer and Center for Integrated Oncology, University Hospital, Cologne, Germany
   Barbara Wappenschmidt & Rita K Schmutzler
5. Department of Obstetrics and Gynecology, Heinrich-Heine-University, Düsseldorf, Germany
   Dieter Niederacher & Ellen Honisch
6. Institute of Human Genetics, Helmholtz Zentrum Muenchen, Neuherberg, Germany
   Peter Lichtner
7. Institute of Virology, Heinrich-Heine-University, Düsseldorf, Germany
   Linda Hartmann & Heiner Schaal
8. Institute of Human Genetics, Center for Molecular Medicine Cologne and Cologne Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases, University of Cologne, Cologne, Germany
   Christian Kubisch
9. Institute of Epidemiology, Helmholtz Zentrum Muenchen, Neuherberg, Germany
   Hans E Wichmann
10. Department of Obstetrics and Gynecology, Carl Gustav Carus University, Dresden, Germany
    Karin Kast
11. Department of Obstetrics and Gynecology, Ulm University, Ulm, Germany
    Helmut Deißler
12. Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany
    Christoph Engel
13. Max-Planck-Institute of Psychiatry, Munich, Germany
    Bertram Müller-Myhsok
14. Department of Human Genetics, University of Würzburg, Würzburg, Germany
    Kornelia Neveling & Detlev Schindler
15. Department of Medical and Molecular Genetics, Kings College, Guy's Hospital, London, UK
    Christopher G Mathew
16. Department of Pediatrics, Wells Center for Pediatric Research, Riley Hospital, Indiana University School of Medicine, Indianapolis, Indiana, USA
    Helmut Hanenberg

Authors

1. Alfons Meindl
2. Heide Hellebrand
3. Constanze Wiek
4. Verena Erven
5. Barbara Wappenschmidt
6. Dieter Niederacher
7. Marcel Freund
8. Peter Lichtner
9. Linda Hartmann
10. Heiner Schaal
11. Juliane Ramser
12. Ellen Honisch
13. Christian Kubisch
14. Hans E Wichmann
15. Karin Kast
16. Helmut Deißler
17. Christoph Engel
18. Bertram Müller-Myhsok
19. Kornelia Neveling
20. Marion Kiechle
21. Christopher G Mathew
22. Detlev Schindler
23. Rita K Schmutzler
24. Helmut Hanenberg

Contributions

The study was designed by A.M., R.K.S. and H. Hanenberg. The screening experiments were performed by H. Hellebrand, D.N., B.W., K.K., H.D. and E.H. under the direction of A.M. Cloning, virus production, transductions and functional complementation tests were set up by C.W., V.E., K.N. and M.F. under the direction of H. Hanenberg and D.S. L.H. and H.S. performed splicing experiments. MALDI-TOF experiments were performed by P.L. under the direction of H.E.W. The statistical analyses were done by B.M.-M., R.K.S. and C.E. C.E. also provided clinical and histopathological data. Control samples were collected by C.K. and H.E.W. The search for families was initiated by M.K. and R.K.S., and families were provided by the GC-HBOC. J.R. and C.G.M. participated in discussing and revising the manuscript. The manuscript was written by A.M., R.K.S., D.N. and H. Hanenberg.

Corresponding authors

Correspondence toAlfons Meindl or Helmut Hanenberg.

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Competing interests

The authors declare no competing financial interests.

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Meindl, A., Hellebrand, H., Wiek, C. et al. Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene.Nat Genet 42, 410–414 (2010). https://doi.org/10.1038/ng.569

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• Received: 05 November 2009
• Accepted: 22 March 2010
• Published: 18 April 2010
• Issue date: May 2010
• DOI: https://doi.org/10.1038/ng.569