{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T15:02:46Z","timestamp":1776870166870,"version":"3.51.2"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated deaths worldwide with an estimated of 900,000 new cases annually. HCC typically arises in patients with chronic liver disease, including hepatitis, cirrhosis, and non-alcoholic fatty liver diseases. Identifying of 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\u2019s cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Forty HCC patients with different etiologies were included in this study. 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, including 10 fresh-frozen samples and 6 FFPE samples. DNA was extracted using the MagCore\u00ae Plus II system. Targeted next-generation sequencing was performed using\n                      <jats:italic>the Illumina AmpliSeq\u2122 Cancer Hotspot Panel v2<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 35 germline mutations were identified across 25 genes. Recurrently altered genes included FGFR3 (100%), PDGFRA (100%), RET (98%), APC (92%), TP53 (88%), and EGFR (75%). In addition, 14 somatic mutations were detected in 13 genes, with frequent alterations observed in APC (100%), ALK (94%), HNF1A (56%), CDKN2A (50%), and HRAS (50%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1699280","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T06:43:01Z","timestamp":1767681781000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification of novel germline and somatic mutations associated with hepatocellular carcinoma by next-generation sequencing"],"prefix":"10.3389","volume":"16","author":[{"given":"Ahmed Baligh","family":"Laaribi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wafa","family":"Babay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdelmalek","family":"Lekired","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bochra","family":"Bouchabou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asma","family":"Mehri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dhouha","family":"Bacha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riadh","family":"Sassi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sana","family":"Ben Slama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rached","family":"Bayar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sahir","family":"Omrani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia","family":"Boujelbene","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rim","family":"Ennaifer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nafaa","family":"Arfa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahlem","family":"Lahmar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hadda-Imene","family":"Ouzari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"116981","DOI":"10.1016\/j.diagmicrobio.2025.116981","article-title":"The TP53 \u201crs 1042522\u201d polymorphism and its association with precancerous cervical lesions progression among Tunisian women","volume":"113","author":"Ben Jemia","year":"2025","journal-title":"Diagnostic Microbiol. 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