1. ¹Section of Cancer Genetics, Institute of Cancer Research, Brookes Lawley Building, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK
2. ²Genetic Epidemiology Division, Cancer Research UK Clinical Centre, St. James's University Hospital, Leeds LS9 7TF, UK
3. ³Cancer Research UK Genetic Epidemiology Unit, Strangeways Research Laboratory Worts Causeway, Cambridge CB1 8RN, UK
4. ⁴Department of Medical Oncology, Division of Medicine, University of New South Wales and Prince of Wales Hospital Randwick, Sydney, Australia
5. ⁵Department of Haematology and Medical Oncology Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002, Australia
6. ⁶Princess Margaret Hospital and University of Toronto, 610 University Avenue, Toronto, ON, Canada M5G 2M9
7. ⁷Department of Radiotherapy and Oncology, University Hospital, V Uvalu 84, 150 06 Prague, Czech Republic
8. ⁸Department of Oncology 5073, Rigshospitalet, Copenhagen, Denmark
9. ⁹Génétique Oncologique EPHE Faculté de Médecine Paris-Sud, UPRESS 1602 and Service d'Urologie, CHU, 94276 Le Kremlin-Bicêtre, France
10. ¹⁰Department of Urological Oncology, Phillips University, Marburg, Germany
11. ¹¹Department of Chemotherapy C and Department of Molecular Genetics National Institute of Oncology, Rath Gyorgy u. 7, H-1122 Budapest, Hungary
12. ¹²Department of Medical Oncology, St James Hospital, Dublin, Ireland
13. ¹³Pathology/Laboratory For Experimental Patho-Oncology, Erasmus University Medical Center Rotterdam/Daniel den Hoed Cancer Center, Josephine Nefkens Institute, 3000 DR Rotterdam, Netherlands
14. ¹⁴Cancer Genetics Laboratory, University of Otago, PO Box 56, Dunedin, New Zealand
15. ¹⁵Department of Oncology, The Norwegian Radium Hospital and Department of Medical Genetics, Rikshospitalet 0027 Oslo, Norway
16. ¹⁶Laboratory of Clinical Genetics, Institute of Clinical Oncology, NN Blokhin Russian Cancer Research Center, Kashirskoye sh., 24, Moscow 115478, Russian Federation
17. ¹⁷Clinical Cancer Research Unit, UICC Familial Cancer and Prevention Project Heuberg 16 CH-4051 Basel, Switzerland
18. ¹⁸Indiana University, Indianapolis, IN, USA
19. ¹⁹Abramson Family Cancer Research Institute, University of Pennsylvania, PA USA
20. ²⁰Clinical Genetics Branch, Division of Cancer Epidemiology & Genetics, National Cancer Institute National Institutes of Health, 6120 Executive Boulevard, Room Rockville, MD 20852- 7231, USA

Correspondence: Dr EA Rapley, E-mail: Liz.raphy@icr.ac.uk

Received 31 October 2003; Revised 13 February 2004; Accepted 25 March 2004; Published online 18 May 2004.

Abstract

Somatic mutations of the KIT gene have been reported in mast cell diseases and gastrointestinal stromal tumours. Recently, they have also been found in mediastinal and testicular germ cell tumours (TGCTs), particularly in cases with bilateral disease. We screened the KIT coding sequence (except exon 1) for germline mutations in 240 pedigrees with two or more cases of TGCT. No germline mutations were found. Exons 10, 11 and 17 of KIT were examined for somatic mutations in 123 TGCT from 93 multiple-case testicular cancer families. Five somatic mutations were identified; four were missense amino-acid substitutions in exon 17 and one was a 12 bp in-frame deletion in exon 11. Two of seven TGCT from cases with bilateral disease carried KIT mutations compared with three out of 116 unilateral cases (P=0.026). The results indicate that somatic KIT mutations are implicated in the development of a minority of familial as well as sporadic TGCT. They also lend support to the hypothesis that KIT mutations primarily take place during embryogenesis such that primordial germ cells with KIT mutations are distributed to both testes.