ArticleHuman molecular genetics2008
Bladder tumour-derived somatic TSC1 missense mutations cause loss of function via distinct mechanisms.
Article in Human molecular genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 55 citations in OpenAlex.
- Neurodevelopmental and Behavioral Profiles in Children with Tuberous Sclerosis Complex: Exploratory Associations with Epilepsy Onset and Cortical Tuber Burden.Journal of clinical medicine · 2026Article
- Article
- Comprehensive analysis of non-synonymous single-nucleotide polymorphism of human TSC1 and TSC2 genes: An in silico approach.PloS one · 2026Article
- Role of TSC1 in physiology and diseases.Molecular and cellular biochemistry · 2021Review
- Bladder perivascular epithelioid cell tumour and tuberous sclerosis complex: a rare association.BMJ case reports · 2021Article
- Mutational Landscape and Environmental Effects in Bladder Cancer.International journal of molecular sciences · 2020Review
- Advances in urinary biomarker discovery in urological research.Investigative and clinical urology · 2020Review
- Mutation of the co-chaperone Tsc1 in bladder cancer diminishes Hsp90 acetylation and reduces drug sensitivity and selectivity.Oncotarget · 2019Article
- Tuberous sclerosis complex is required for tumor maintenance in MYC-driven Burkitt's lymphoma.The EMBO journal · 2018Article
- SLC14A1: a novel target for human urothelial cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2017Review
- Tsc2 disruption in mesenchymal progenitors results in tumors with vascular anomalies overexpressingeLife · 2017Article
- Is 5´-AMP-Activated Protein Kinase Both Jekyll and Hyde in Bladder Cancer?International neurourology journal · 2015Review
- The discovery of potent ribosomal S6 kinase inhibitors by high-throughput screening and structure-guided drug design.Oncotarget · 2013Article
- Diverse mechanisms of AKT pathway activation in human malignancy.Current cancer drug targets · 2013Review
- Immunohistochemical loss of succinate dehydrogenase subunit A (SDHA) in gastrointestinal stromal tumors (GISTs) signals SDHA germline mutation.The American journal of surgical pathology · 2013Article
- Determination of the consequences of VHL mutations on VHL transcripts in renal cell carcinoma.International journal of oncology · 2012Article
- Tuberous sclerosis complex 1: an epithelial tumor suppressor essential to prevent spontaneous prostate cancer in aged mice.Cancer research · 2010Article
- Mammalian target of rapamycin (mTOR) regulates cellular proliferation and tumor growth in urothelial carcinoma.The American journal of pathology · 2010Article
- FOXO3a regulates glycolysis via transcriptional control of tumor suppressor TSC1.The Journal of biological chemistry · 2010Article
- Molecular genesis of non-muscle-invasive urothelial carcinoma (NMIUC).Expert reviews in molecular medicine · 2010Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
More than 50% of transitional cell carcinomas of the bladder show loss of heterozygosity of a region spanning the TSC1 locus at 9q34 and mutations of TSC1 have been identified in 14.5% of tumours. These comprise nonsense mutations, splicing mutations, small deletions and missense mutations. Missense mutations are only rarely found in the germline in TSC disease. Therefore, we have examined six somatic missense mutations found in bladder cancer to determine whether these result in loss of function. We describe loss of function via distinct mechanisms. Five mutations caused mutually exclusive defects at mRNA and protein levels. Of these, two mutations caused pre-mRNA splicing errors that were predicted to result in premature protein truncation and three resulted in markedly reduced stability of exogenous TSC1 protein. Primary tumours with aberrant TSC1 pre-mRNA splicing were confirmed as negative for TSC1 expression by immunohistochemistry. Expression was also significantly reduced in a tumour with a TSC1 missense mutation resulting in diminished protein half-life. A single TSC1 missense mutation identified in a tumour with retained heterozygosity of the TSC1 region on chromosome 9 caused an apparently TSC2- and mTOR-independent localization defect of the mutant protein. We conclude that although TSC1 missense mutations do not play a major role in causation of TSC disease, they represent a significant proportion of somatic loss of function mutations in bladder cancer.
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