Genomic profiling of AKT1 and NRAS mutations using NGS in Egyptian hepatocellular carcinoma

Hepatocellular carcinoma (HCC) remains a major health burden in Egypt, with underlying molecular mechanisms still poorly defined. This study aimed to characterize somatic mutations in AKT1 and NRAS genes using targeted next-generation sequencing in Egyptian HCC patients. Cell Tumor DNA (ct DNA) from 50 patients, divided into 25 HCC patients, were classified according to Barcelona clinic Liver Cancer (BCLC) staging alongside HCV-infected and normal controls, was analyzed using the Ion AmpliSeq Cancer Hotspot Panel. Mutational profiles were verified using the Integrative Genomics Viewer and functionally annotated via different cancer databases. A total of 16 somatic mutations were identified (12 in AKT1, 4 in NRAS). The most frequent AKT1 mutation was p.Asp32Glu, observed in multiple clinical groups. Other variants, including p.Glu40Gly and p.Asn31Ile, affected conserved regions of the kinase domain. AKT1 mutations were more prevalent in intermediate and advanced HCC stages, suggesting a role in tumor progression. In contrast, NRAS mutations were rare and evenly distributed across stages, with limited clinical correlation. Functional predictions supported the potential pathogenicity of several AKT1 and NRAS variants. This study highlights a higher frequency and diversity of AKT1 mutations in Egyptian HCC patients, particularly in progressive disease stages, supporting their potential role in HCC development and progression. These findings advocate for expanded molecular profiling in HCC and suggest AKT1 as a promising target for personalized therapy.