Identification of novel germline and somatic mutations associated with hepatocellular carcinoma by next‑generation sequencing
This study identified novel germline and somatic mutations associated with hepatocellular carcinoma in a Tunisian cohort, highlighting key molecular drivers of hepatocarcinogenesis.
Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated deaths worldwide with an estimated 900,000 new cases annually. HCC typically arises in patients with chronic liver disease, including hepatitis, cirrhosis, and non-alcoholic fatty liver diseases. Identifying the main driver genetic alterations in oncogenic genes is essential for understanding HCC pathogenesis and defining prognostic biomarkers in high-risk patients. This study aimed to identify both germline and somatic mutations associated with HCC in a Tunisian patient’s cohort. Methods: Forty HCC patients with different etiologies were included. Peripheral blood samples were collected from 24 patients with advanced-stage HCC. Paired tumor and adjacent non-tumoral liver tissue samples were obtained from 16 early-stage HCC patients undergoing hepatic resection. DNA was extracted and targeted next‑generation sequencing was performed using the Illumina AmpliSeq™ Cancer Hotspot Panel v2. Results: A total of 35 germline mutations were identified across 25 genes. Recurrently altered genes included FGFR3, PDGFRA, RET, APC, TP53, and EGFR. Additionally, 14 somatic mutations were detected in 13 genes, with frequent alterations in APC, ALK, HNF1A, CDKN2A, and HRAS. Conclusion: This study offers the first comprehensive overview of novel germline and somatic mutations in Tunisian HCC patients, representing a North African cohort, and highlights key molecular drivers of hepatocarcinogenesis. These findings support the integration of genetic profiling into clinical practice to enhance early diagnosis and guide personalized therapies.
Identification of novel driver mutations in HCC may improve early diagnosis and enable personalized therapies.
Evidence level: Korai humán adat. Kis vagy feltáró emberi adat.
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