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Table 2 Main molecular alterations in HCC according to molecular subtypes adapted from the Cancer Genome Atlas Research Network [40]

From: Angiogenesis and immune checkpoint inhibitors as therapies for hepatocellular carcinoma: current knowledge and future research directions

Molecular subtypeGenetic featuresEpigenetic featuresOther characteristics
iCluster 1
36%
Few CTNNB1 mutations
Low expression of TERT
Overexpression of proliferation markers
microRNA signature
mir-122 silencing
High expression of miR-181A
Young age
Asian patients
Female patients
Normal Weight
High grade
Poor prognosis
iCluster 2
30%
High expression of TERT
High expression of CTNNB1
HNF1A mutations
CDKN2A silencingLow grade
Low microvascular invasion
iCluster 3
34%
Chromosomal instability
17p loss
TP53 mutations
High activation of CTNNB1
High expression of TERT
Activation of VEGF-A pathway
PTEN inactivation
CDKN2A silencing
CPG Island hypomethylation
Frequencies of most prevalent alterations in the whole cohortTERT mutations 44%
TP53 mutations 31%
CTNNB1 mutations 27%
CDKN2A deletion 13%
APOB mutations 10%
AXIN1 mutations 8%
ARID1A mutations 7%
CDKN2A silencing 54%