Table 7.

Somatic (S) mutations affecting coding (c) and non-coding (nc) regions of pro-apoptotic genes in primary liver cancer

Gene	Protein	Genetic mutation	G/S	Region	Protein mutation	Functional consequences	Clinical consequences	Studies	References
CASP8	Caspase-8	c.1225_1226 delTG	S	c	Val410Phefs*28.	Loss of function	Probably chemoresistance	HCC patients	[154]
CDKN2A	CDKN2A	c.248G>A	S	c	His83Tyr	Moderate	Poor prognosis	HCC patients	[119]
		g.21971148_ 21971155del	S	c	Ala68Glufs*49	High	Poor prognosis	HCC patients	[119]
		c.263C>A	S	c	Glu88*	High	Poor prognosis	HCC patients	[119]
		g.21974672del	S	c	Gly52Valfs*77	High	Poor prognosis	HCC patients	[119]
		g.21974711_ 21974728del	S	c	Glu33_Asn 39delinsAsp	High	Poor prognosis	HCC patients	[119]
		c.72C>G	S	c	Arg24Pro	Moderate	Poor prognosis	HCC patients	[119]
		c.36G>T	S	c	Ser12*	High	Poor prognosis	HCC patients	[119]
RB1	RB1	c.381A>T	S	c	Ser127_splice	ND	Early recurrence after resection	HCC patients	[155]
		c.508G>T	S	c	Glu170*	Loss of function	Early recurrence after resection	HCC patients	[155]
		c.646delT	S	c	Phe216fs	ND	Early recurrence after resection	HCC patients	[155]
		c.763C>T	S	c	Arg255*	Loss of function	Early recurrence after resection	HCC patients	[155]
		c.979A>T	S	c	Lys327*	Loss of function	Early recurrence after resection	HCC patients	[155]
		c.1421G>A	S	c	Ser474Asn	ND	Early recurrence after resection	HCC patients	[155]
		c.1472T>C	S	c	Leu491Pro	ND	Early recurrence after resection	HCC patients	[155]
		c.1654C>T	S	c	Arg552*	Loss of function	Early recurrence after resection	HCC patients	[155]
		c.2120delC	S	c	Ser707fs	ND	Early recurrence after resection	HCC patients	[155]
TP53	p53	c.747G>T	S	c	Arg249Ser	Loss of function	Poor prognosis	HCC patients	[143]
		c.469G>T	S	c	Val157Phe	Loss of function	Poor prognosis	HCC patients	[143]
		c.743G>A	S	c	Arg248Gln	Loss of function	Doxorubicin resistance	HCC in vitro	[144]
			S	c	1-132del (truncated variant Δ133p53)	Dominant negative	Poor outcome, 5-FU resistance	CCA patients	[150]       [151]
TP63	p63		S	c	1-62del (truncated variant ΔNp63)	Gain of function (antiapoptotic-effect)	Doxorubicin and mitoxantrone resistance. Shorter OS	HCC patients	[147]       [148]
TP73	p73		S	c	1-72del (truncated variant ΔNp73)	Gain of function (antiapoptotic-effect)	Shorter OS	HCC patients	[147]

Data obtained from cBioportal database and referred literature. Functional consequences are based on VEP (Variant Effect Predictor; https://www.ensembl.org/vep) impact: High means that the variant is supposed to cause a high disruptive impact in the protein, which is likely to cause loss of function; Moderate means that the variant may be not disruptive, but results in a decrease effectiveness of the encoded protein; Modifier is usually referred to non-coding variants, whose impact is difficult to determine, although they can be involved in transcription or splicing changes. CCA: cholangiocarcinoma; HCC: hepatocellular carcinoma; 5-FU: 5-fluorouracil; OS: overall survival; ND: not determined