Table 2 Commonly aberrant genes in hepatocellular carcinoma

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]

PRI-724[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]

[114]

BIBF 1120 [114]

Dovitinib [114]

Lenvatinib [114]