Table 9.

Somatic (S) mutations affecting coding (c) and non-coding (nc) regions of genes related to tumor microenvironment in primary liver cancer

Gene	Protein	G/S	Region	Genetic mutations	Protein mutations	Functional consequences	Clinical consequences	Studies	References
IL6	IL6	S	c	c.179T>A	Ile60Asn	Moderate	Neutral	TCGA-LIHC	TCGA
		S	c	c.83C>T	Ala28Val	Moderate	Neutral	TCGA-LIHC	TCGA
		S	nc	c.20-6C>T	Splice region variant	Modifier	Neutral	TCGA-LIHC	TCGA
		S	nc	c.243+169T>G	Intron	Modifier	ND	TCGA-LIHC	TCGA
MMP2	MMP2	S	c	c.648G>T	Lys216Asn	Moderate	ND	TCGA-LIHC	TCGA
		S	c	c.1160C>G	Pro387Arg	Moderate	ND	TCGA-CHOL	TCGA
		S	c	c.85G>A	Ala29Thr	Moderate	Pathogenic	TCGA-LIHC	TCGA
		S	nc	c.-75-3345G>A	Intron	Modifier	Pathogenic	TCGA-LIHC	TCGA
CXCR4	CXCR4	S	c	c.664A>T	Ile226Phe	Moderate	Pathogenic	TCGA-LIHC	TCGA
		S	nc	c.-55C>A	5’UTR	Modifier	ND	TCGA-LIHC	TCGA
LOX	LOX	S	c	c.1144C>T	Pro382Ser	Moderate	Pathogenic	TCGA-LIHC	TCGA
		S	c	c.850T>A	Tyr284Asn	Moderate	Pathogenic	TCGA-LIHC	TCGA
		S	nc	c.*42T>A	3’UTR	Modifier	Pathogenic	TCGA-LIHC	TCGA

Data obtained from TCGA database. 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. ND: not determined; TCGA: the cancer genome atlas; TCGA-LIHC: the cancer genome atlas - liver hepatocellular carcinoma; TCGA-CHOL: the cancer genome atlas - cholangiocarcinoma