• What is TSC1?
  • TSC1 in Bladder Cancer
  • TSC1 c.1907_1908del (E636fs)
  • Clinical Trials

TSC1

Tuberous sclerosis 1 (TSC1) encodes for a protein, hamartin, that interacts with a protein encoded by the TSC2 gene, tuberin (Genetics Home Reference 2013). TSC1 acts as a tumor suppressor, through regulation of the mTOR pathway, which is involved in cell proliferation (Genetics Home Reference 2013; Sjodahl et al. 2011).

TSC1 interacts with mTOR pathway proteins, and a bladder cancer patient’s TSC1-mutated tumor has been observed to be sensitive to the mTOR inhibitor everolimus (Iyer et al. 2012).

Related Pathways

Contributors: David Solit, M.D.

Suggested Citation: Solit, D. 2015. TSC1. My Cancer Genome https://www.padiracinnovation.org/content/disease/bladder-cancer/tsc1/?tab=0 (Updated December 7).

Last Updated: December 7, 2015

TSC1 in Bladder Cancer

Mutations in TSC1 are observed in 7–12% of bladder cancers. The frequency of mutations is the same for low grade, non-invasive, and high grade, invasive, tumors (COSMIC; Iyer et al. 2012; Sjodahl et al. 2011​).

mTOR inhibitors have been identified as potential therapies for TSC1-mutated bladder cancers (Iyer et al. 2012). Further study is needed to explore this and other strategies for use of targeted therapeutics in bladder cancer.

Contributors: David Solit, M.D.

Suggested Citation: Solit, D. 2013. TSC1 in Bladder Cancer. My Cancer Genome https://www.padiracinnovation.org/content/disease/bladder-cancer/tsc1/ (Updated February 12).

Last Updated: February 12, 2013

TSC1 c.1907_1908del (E636fs) Mutation in Bladder Cancer

Properties
Location of mutation Exon 15
Frequency of TSC1 mutations in bladder cancer 11.7% (Sjodahl et al. 2011​)
Frequency of E636fs mutation among TSC1-mutated bladder cancers Observed 1 time (Iyer et al. 2012)
Implications for Targeted Therapeutics
mTOR inhibitors Confers increased sensitivitya

The E636fs mutation results in a frameshift and the introduction of a premature stop codon into the TSC1 gene. This mutation occurs within exon 15.

a A case report and in vitro studies have shown that mutations in the TSC1 gene may confer sensitivity to mTOR inhibitors (Iyer et al. 2012). These findings have yet to be confirmed in clinical trials.

Contributors: David Solit, M.D.

Suggested Citation: Solit, D. 2013. TSC1 c.1907_1908del (E636fs) Mutation in Bladder Cancer. My Cancer Genome https://www.padiracinnovation.org/content/disease/bladder-cancer/tsc1/237/ (Updated February 12).

Last Updated: February 12, 2013

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