Table 2.

Location of HBV DNA integrations in coding regions of the human genome by whole exome sequencing

Patient no.	Patient group	Chimeric HBV human reads (n)	Human chromosome no.	Human genes	Gene description*	Location of HBV integrants within human genes	Distance to proximal exons†	Potential downstream effect‡
HBV DNA integration in intronic or exonic regions of human genome
14	1	1	Chr_21	COL18A1§	Collagene XVIII	Intronic	14 091	Regulation of angiogenesis and tumour growth
22	1	1	Chr_16	LMF1§	Lipoprotein maturation factor 1	Intronic	7157	Protein involved in lipoprotein metabolism
33	2	1	Chr_19	ADGRL1§	G-protein coupled receptors	Intronic	7310	Involved in cell adhesion and signal transduction
39	3	1	Chr_17	ELAC2	Ribonuclease Z	Intronic	15¶	Altered levels in liver cancer
40	3	2	Chr_11	IFITM1	Interferon-induced antiviral protein	Intronic	44 and 72**	B cell receptor signalling pathway
44	2	1	Chr_17	NUP85	Nuclear pore complex	Intronic	6**	RNA transport pathway; altered levels are associated with negative prognosis in liver cancer
62	3	8	Chr_12	ANKRD52§	Ankyrin repeat domain	Intronic	6 and 32**	Altered levels are associated with negative prognosis in liver cancer
75	2	1	Chr_2	AGBL5§	Metallocarboxypeptidase	Intronic	80¶	Altered levels are associated with negative prognosis in liver cancer
83	2	2	Chr_5	NR3C1§	Glucocorticoid receptor	Exonic	0	Regulation of inflammatory responses
84	3	2	Chr_4	CYP2U1	Cytochrome P450	Intronic	99¶	Drug metabolism
HBV DNA integration in intergenic regions of human genome
2	3	2	Chr_9	n.a.	n.a.	Intergenic	458 413	n.a.
10	3	1	Chr_5	n.a.	n.a.	Intergenic	69 228	n.a.
68	3	1	Chr_18	n.a.	n.a.	Intergenic	158 827	n.a.
81	3	2	Chr_10	n.a.	n.a.	Intergenic	17 498	n.a.

The table displays the 12 HBV DNA integration events observed in the 10 patients localised in intronic or exonic regions of human genome and the 4 HBV DNA integration events localised in intergenic regions.

*Genes information is retrieved by GeneCards: The Human Gene Database.

†Distance in nucleotides of HBV integrants to the most proximal exons.

‡Genes’ cellular role is retrieved from the Human Protein Database and from KEGG PATHWAY Database.

§These genes were involved in HBV DNA integration events as reported in Virus Integration Sites Database (https://bioinfo.uth.edu/VISDB/index.php/homepage).

¶HBV integrants reside in proximity (<100 nucleotides) to donor site, localised at 5’ end of introns and crucial for RNA splicing.

**HBV integrants reside within or in proximity (<50 nucleotides) to branching site, a crucial region localised at 3’ end of introns and crucial for RNA splicing.

n.a., not applicable.