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Published on: November 28, 2015
Absence of AKT1 mutations in glioblastoma
Fonnet E Bleeker1, Simona Lamba, Carlo Zanon
1Neurosurgical Center Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. f.e.bleeker@amc.uva.nl
Background:
Oncogenic activation of the PI3K signalling pathway plays a pivotal role in the development of glioblastoma multiforme (GBM). A central node in PI3K downstream signalling is controlled by the serine-threonine kinase AKT1. A somatic mutation affecting residue E17 of the AKT1 gene has recently been identified in breast and colon cancer. The E17K change results in constitutive AKT1 activation, induces leukaemia in mice, and accordingly, may be therapeutically exploited to target the PI3K pathway. Assessing whether AKT1 is activated by somatic mutations in GBM is relevant to establish its role in this aggressive disease.
Methodology/Principal Findings:
We performed a systematic mutational analysis of the complete coding sequence of the AKT1 gene in a panel of 109 tumor GBM samples and nine high grade astrocytoma cell lines. However, no somatic mutations were detected in the coding region of AKT1.
Conclusions/Significance:
Our data indicate that in GBM oncogenic deregulation of the PI3K pathway does not involve somatic mutations in the coding region of AKT1.
Insights
Glioblastoma multiforme (GBM) PI3K pathway deregulation does not involve AKT1 gene mutations. Researchers found no somatic mutations in the AKT1 coding region in GBM tumors, suggesting alternative mechanisms for pathway activation.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The PI3K signaling pathway is crucial in glioblastoma multiforme (GBM) development.
- AKT1 is a key downstream kinase in this pathway.
- A specific AKT1 mutation (E17K) found in other cancers causes constitutive activation.
Purpose of the Study:
- To investigate if AKT1 somatic mutations contribute to GBM pathogenesis.
- To determine the role of AKT1 in the PI3K pathway deregulation in GBM.
Main Methods:
- Systematic mutational analysis of the entire AKT1 coding sequence.
- Analysis of 109 GBM tumor samples and 9 high-grade astrocytoma cell lines.
Main Results:
- No somatic mutations were detected in the coding region of the AKT1 gene.
- This finding was consistent across all analyzed GBM samples and cell lines.
Conclusions:
- Somatic mutations in the AKT1 coding region are not a mechanism for PI3K pathway deregulation in GBM.
- Alternative mechanisms likely drive AKT1 activation and PI3K pathway dysregulation in glioblastoma.
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