Novel Mutations in AKT1 Gene in Prostate Cancer Patients in Jordan

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• The AKT1 oncogene plays a key role in the PI3K/AKT1 pathway, implicated in various cancers.
• The AKT1 E17K hotspot mutation is frequently studied, but its incidence is low in prostate cancer (PC).
• Limited research exists on AKT1 mutations in Jordanian PC patients, especially outside the E17K hotspot.

Purpose of the Study:

• To investigate genetic alterations in the AKT1 Pleckstrin homology (PH) domain in Jordanian PC patients.
• To extend genetic screening to AKT1 gene exons 3 and 4, beyond the common E17K hotspot.
• To determine the frequency and types of AKT1 mutations in this cohort.

Main Methods:

• Genomic DNA extraction from 84 Formalin-Fixed Paraffin-Embedded (FFPE) PC samples from Jordan.
• Polymerase Chain Reaction (PCR) amplification of targeted AKT1 gene exons 3 and 4.
• DNA sequencing to identify genetic variations within the targeted exons.

Main Results:

• A high frequency of AKT1 mutations was detected in exon 4, including nine missense and two synonymous mutations.
• Two novel missense mutations (N53Y and Q59K) were identified in the AKT1 PH domain.
• No mutations were found in the AKT1 E17K hotspot; two synonymous mutations were found in exon 3.

Conclusions:

• Prostate cancer patients in Jordan exhibit a high prevalence of AKT1 mutations, distinct from the E17K hotspot.
• Novel mutations in the AKT1 PH domain suggest alternative mechanisms driving PC development.
• Further research into non-hotspot AKT1 mutations is crucial for understanding PC pathogenesis.