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Mutation of the 9q34 gene TSC1 in sporadic bladder cancer

Abstract

Deletions involving chromosome 9 occur in more than 50% of human bladder cancers of all grades and stages. Most involve loss of the whole chromosome or of an entire chromosome arm but some small deletions are found which can be used to define critical regions which may contain tumour suppressor genes. We have localized such a critical region of deletion at 9q34 between the markers D9S149 and D9S66, an interval which contains the Tuberous Sclerosis gene TSC1. Single strand conformation polymorphism (SSCP) and sequence analysis of TSC1 in bladder tumours and cell lines with 9q34 loss of heterozygosity (LOH) has identified five mutations in retained TSC1 alleles. Our results support the hypothesis that TSC1 can act as a bladder tumour suppressor gene.

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Abbreviations

TCC:

transitional cell carcinoma

LOH:

loss of heterozygosity

SSCP:

single strand conformation polymorphism

TSC:

tuberous sclerosis complex

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Acknowledgements

The authors thank Hani Gabra for providing DNA samples from ovarian tumours and Sue Povey, Jonathan Wolfe and Janet Young for their assistance both with materials and with helpful discussions. This work was supported by the Imperial Cancer Research Fund and Marie Curie Cancer Care.

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Hornigold, N., Devlin, J., Davies, A. et al. Mutation of the 9q34 gene TSC1 in sporadic bladder cancer. Oncogene 18, 2657–2661 (1999). https://doi.org/10.1038/sj.onc.1202854

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