Table 2.

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

Molecular subtype	Genetic features	Epigenetic features	Other 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 silencing	Low 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 cohort	TERT mutations 44% TP53 mutations 31% CTNNB1 mutations 27% CDKN2A deletion 13% APOB mutations 10% AXIN1 mutations 8% ARID1A mutations 7%	CDKN2A silencing 54%	–