Mutation of the 9q34 gene TSC1 in sporadic bladder cancer

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 gene...

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Published inOncogene Vol. 18; no. 16; pp. 2657 - 2661
Main Authors HORNIGOLD, N, DEVLIN, J, DAVIES, A. M, AVEYARD, J. S, HABUCHI, T, KNOWLES, M. A
Format Journal Article
LanguageEnglish
Published Basingstoke Nature Publishing 22.04.1999
Nature Publishing Group
Subjects
Biological and medical sciences
Bladder
Bladder cancer
Cell physiology
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
Chromosome 9
Chromosomes
Chromosomes, Human, Pair 9
Conformation
DNA Primers
Exons
Fundamental and applied biological sciences. Psychology
Gene polymorphism
Genes, Dominant
Genes, Tumor Suppressor
Genetic Linkage
Heterozygosity
Humans
Loss of Heterozygosity
Models, Genetic
Molecular and cellular biology
Mutation
Polymorphism, Single-Stranded Conformational
Proteins - genetics
Sequence analysis
Sequence Deletion
TSC1 gene
Tuberous sclerosis
Tumor suppressor genes
Tumor Suppressor Proteins
Tumors
Urinary Bladder Neoplasms - genetics
Genetic mapping
Human
Urinary system disease
Sporadic
Urinary bladder
Loss of heterozygosity
Deletion
Tumor
Bladder disease
Mutation
Chromosome C9
Tumor suppressor gene
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Summary: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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ISSN:0950-9232
1476-5594
DOI:10.1038/sj.onc.1202854