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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
11:15

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Published on: September 20, 2016

AKT1 mutations in bladder cancer: identification of a novel oncogenic mutation that can co-operate with E17K

J M Askham1, F Platt, P A Chambers

  • 1Cancer Research UK Clinical Centre, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, UK.

Oncogene
|October 6, 2009
PubMed

Insights

The AKT1 E17K mutation, known in other cancers, was found in bladder tumors. This activating mutation in AKT1 may play a role in bladder cancer development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • The phosphatidylinositol-3-kinase (PI3K)-AKT pathway is crucial in cancer development and is frequently activated.
  • Activating mutations in AKT1 have been identified in various cancers, including breast, colorectal, ovarian, and lung cancers.

Purpose of the Study:

  • To investigate the presence and role of AKT1 mutations in bladder cancer.
  • To characterize a novel AKT1 mutation and its functional impact on AKT activation.

Main Methods:

  • Screening of bladder cancer cell lines and tumors for AKT1 mutations.
  • Functional analysis of mutant AKT1 in cell lines to assess constitutive activation.
  • Evaluation of transforming activity of AKT1 mutations in NIH3T3 cells.

Main Results:

  • The AKT1 G49A (E17K) mutation was identified in 2/44 bladder cancer cell lines (4.8%) and 5/184 bladder tumors (2.7%).
  • Cell lines with mutant AKT1 exhibited constitutive AKT1 activation.
  • A novel AKT1 mutation, G145A (E49K), was discovered, which also enhanced AKT activation and demonstrated transforming activity, albeit weaker than E17K.
  • Tandem E17K and E49K mutations suggested cooperative effects on AKT1 activation.

Conclusions:

  • The AKT1 E17K mutation occurs in bladder cancer, suggesting its involvement in the pathogenesis of this cancer type.
  • The novel E49K mutation also contributes to AKT activation and has transforming potential.
  • Co-occurring AKT1 mutations may enhance oncogenic signaling in bladder cancer.

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