Table III.

Summary of linkage studies between HCC and AID/APOBECs.

Protein	Experimental targets	Indication	Reference
A1	TM, TR	All of the TM and one TR had liver dysplasia. 8/35 TM developed HCC.	95
A1	TM, TR	The aberrant editing markedly reduced levels of protein expression by the tumor suppressor gene, NAT1.	96
A2	TM	HCC developed in 2/20 A2 TM at 72 weeks of age. Significantly high frequencies of nucleotide alterations in EIF4G2 and PTEN genes were observed in hepatocytes.	97
A3	CL, HCCT	C-terminally truncated HBx mutants generated by A3 enhanced the colony forming ability and proliferative capacity of neoplastic cells. A3B upregulated HSF1.	37
A3A	CL	A3A led to induction of cellular DNA breaks and activation of damage responses in a deaminase-dependent manner. A3A expression induced cell cycle arrest.	98
AID	CL, HCCT	The majority of liver tissues with AID upregulation contained multiple genetic changes in the p53 gene. Aberrant activation of AID in hepatocytes resulted in accumulation of multiple genetic alterations in the p53 gene.	46
AID	TM	HCC developed in 27% of tissue-nonspecific alkaline phosphatase-AID TM at the age of 90 weeks. The HCC expressed α-fetoprotein and possessed deleterious mutations in the tumor suppressor gene, TRP53.	94

AID, activation-induced cytidine deaminase; APOBEC, apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like; TM, transgenic mice; TR, transgenic rabbit; CL, cell line; CH, chronic hepatitis; LC, liver cirrhosis; HCC, hepatocellular carcinoma; HCCT, HCC tissue; NAT1, novel A1 target no 1; EIF4G2, eukaryotic translation initiation factor 4 γ, 2; PTEN, phosphatase and tensin homolog; HBx, hepatitis B virus X; HSF1, heat shock transcription factor 1; TRP53, tumor protein P53.