Abstract 4014: APOBEC3B promotes hepatocarcinogenesis and metastasis through novel deaminase-independent activity

Abstract APOBEC3B (A3B), a cytidine deaminase, is known to play important roles in creating de novo genomic C-to-T mutations in cancers and contribute to induction of genomic instability. In this study, we evaluated the roles of A3B in the progression and metastasis of human hepatocellular carcinoma (HCC). Using whole-transcriptome and whole-exome sequencing and quantitative real-time PCR, we found that A3B was overexpressed in human HCCs and A3B expression was significantly correlated with the proportion of genomic C-to-A and G-to-T mutations. Upon clinicopathological correlation, higher A3B expression was associated with more aggressive tumor behavior. Wild-type A3B (wt-A3B) overexpression in HCC cells promoted cell proliferation, and cell migratory and invasive abilities in vitro, and tumorigenicity and metastasis in vivo. On the other hand, knockdown of A3B suppressed cell proliferation, migratory and invasive abilities of HCC cells with high endogenous A3B level. However, to our surprise, overexpression of A3B deaminase-dead double mutant (E68A/E255Q) led to similar results as wt-A3B in HCC both in vitro and in vivo. Furthermore, overexpression of wt-A3B and mutant A3B both enhanced cell cycle progression in HCC cells. Altogether, our data demonstrated a novel deaminase-independent role of A3B in contributing to HCC tumorigenesis and metastasis. Citation Format: Irene O L Ng, Wei Ma, Daniel WH Ho, Karen MF Sze, Yue M. Tsui, Lo K. Chan, Joyce MF Lee. APOBEC3B promotes hepatocarcinogenesis and metastasis through novel deaminase-independent activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4014.