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Table 2 Commonly aberrant genes in hepatocellular carcinoma

From: The biology of Hepatocellular carcinoma: implications for genomic and immune therapies

Gene Aberration Frequency (% of patients) Pathway Function Examples of Potential Targeted Agenta
TERT promoter About 60% [46, 47] Telomere maintenance Adds telomere repeats (TTAGGG) onto chromosome ends, compensating for the erosion of protective telomeric ends that is a normal part of cell division [110]  
TP53 Mutations: 3–40%
Loss: 2–15% [20,21,22]
P53 pathway Tumor suppressor [23] Bevacizumab [33]
TP53 gene regulates the expression of VEGF-A. Anti-angiogenic agents were correlated with longer PFS in patients harboring TP53- mutant tumors [32] Ramucirumab [111]
Sorafenib [13]
Wee-1 inhibitors [36]
CTNNB1 Mutations: 11–41% [20,21,22] Wnt pathway Regulates cell adhesion, growth, and differentiation [23]. BBI608 is a potent small molecule inhibitor [112]
Sulindac [113]
AXIN1 Mutations 5–19% [20,21,22] Wnt pathway Regulates cell adhesion, growth, and differentiation. Small molecule inhibitor XAV939 [31]
ARID1A Mutations 4–17% [20,21,22, 37] Chromatin remodeling Transcriptional activation and repression of selected genes via chromatin remodeling [23]
CDKN2A Deletion 7–8% [18, 20] Cell cycle Tumor suppressor gene promotes cell cycle arrest in G1 and G2 phases. Suppresses MDM2 [23] CDK4/6 inhibitor palbociclib [13]
ARID2 Mutations-5-7% [18, 21, 37] Chromatin remodeling Tumor suppressor gene with a role in the transcriptional activation and repression of selected genes [23]
RPS6KA3 Mutations 4–7% [18, 22] Dual function-regulation of the MAPK/ERK and mTOR signaling Mediates stress-induced and mitogenic activation of transcription factors and cellular differentiation, proliferation, and survival [23].
CCND1 Alterations (focal amplifications or deletions) 4.7%–7% [18, 41] P53 pathway Cell cycle Functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle progression [23]. Palbociclib [13]
FGF3, FGF4 or FGF19 Alterations (focal amplification or deletions) 4–5.6% [18, 41] FGF pathway FGF family members possess broad mitogenic and cell survival activities and are operative in tumor growth and invasion, and tissue repair [23]. Brivanib [44]
BIBF 1120 [114]
Dovitinib [114]
Lenvatinib [114]
  1. aFor many of these targeted agents, it is not yet clear if use of the agent in patients with the cognate aberrant genes is effective