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AKT2 Exon 3 Variants and Their Prevalence in Prostate Cancer Patients: Insights from a Jordanian Clinical Cohort
Nuseibah Rahahlah1, Zina Al-Alami1, Mohammed S Alorjani2
1Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, P.O. Box 115, Amman 19111, Jordan.
Abstract:
The AKT2 gene, located on chromosome 19, encodes a protein involved in key cellular processes like metabolism, proliferation, and survival. Abnormalities in the PI3K/AKT pathway, including AKT2, contribute to tumor progression. AKT2 promotes cell survival, growth, and resistance to therapy. Overexpression or hyperactivation of AKT2 is linked to prostate cancer (PC) development, making it a potential therapeutic target. This study aimed to investigate the frequency and distribution of AKT2 variants in a cohort of Jordanian men diagnosed with PC and to evaluate the relationship between these genetic variations and clinicopathological parameters, including age, tumor stage, PSA levels, and Gleason score. Formalin-fixed paraffin-embedded (FFPE) tissue samples (n = 123) were collected from Jordanian patients diagnosed with prostate adenocarcinoma. The collected samples underwent DNA extraction, followed by PCR amplification. Subsequently, exon 3 of AKT2 was sequenced. The prevalence of AKT2 mutations was 5.7% in the population studied. Six mutations were identified: two missense mutations (Pro51Ser and Gly33Ser), two synonymous, one splice acceptor, and one intron variant. The variants were not significantly correlated with clinical parameters; however, the prevalence of the AKT2 mutations suggests potential relevance to PC pathogenesis. The prevalence of AKT2 mutations in the current cohort suggested a potential role of AKT2 in PC pathogenesis in the Jordanian population. Further genetic studies covering the whole AKT2 gene and the downstream pathway are required for a better understanding of PC genetics.
Insights
This study found 5.7% AKT2 gene mutations in Jordanian prostate cancer patients. These AKT2 variants may play a role in prostate cancer development, warranting further investigation.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- The AKT2 gene is crucial for cellular functions and its abnormalities are linked to tumor progression.
- AKT2 plays a role in cell survival, growth, and therapy resistance.
- AKT2 overexpression is associated with prostate cancer (PC) development, indicating its potential as a therapeutic target.
Purpose of the Study:
- To determine the frequency and distribution of AKT2 gene variants in Jordanian men with PC.
- To explore the association between AKT2 genetic variations and clinicopathological parameters in prostate cancer.
Main Methods:
- DNA extraction from 123 formalin-fixed paraffin-embedded (FFPE) tissue samples of Jordanian prostate adenocarcinoma patients.
- Polymerase chain reaction (PCR) amplification of AKT2 exon 3.
- Sequencing of AKT2 exon 3 to identify genetic variations.
Main Results:
- A prevalence of 5.7% for AKT2 mutations was observed in the studied Jordanian cohort.
- Six distinct mutations were identified, including missense, synonymous, splice acceptor, and intron variants.
- No significant correlation was found between AKT2 variants and clinicopathological parameters like age, tumor stage, PSA levels, or Gleason score.
Conclusions:
- The identified prevalence of AKT2 mutations suggests a potential role in prostate cancer pathogenesis within the Jordanian population.
- Further comprehensive genetic studies of the entire AKT2 gene and its downstream pathways are necessary.
- Understanding AKT2's role can contribute to better insights into prostate cancer genetics and potential therapeutic strategies.
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