Molecular characterization of the A52 murine hepatocellular carcinoma cell line.

BACKGROUND

To combat hepatocellular carcinoma (HCC) disease heterogeneity and growing mortality, there is an urgent need for targeted and personalized therapeutics. While syngeneic mouse models are commonly used for preclinical validation of these therapeutics, the lack of genetically characterized murine cell lines adds uncertainty to the study of drug-gene interactions in these models. We previously generated a novel murine cell line, A52, from a diethylnitrosamine (DEN)-induced adiponectin-knockout mouse model. Here, we present a comprehensive genomic and transcriptomic characterization of the A52 cell line.

METHODS

A52 cells were grown in various culture medium compositions to investigate robustness to simple media. Whole-genome sequencing (WGS) and RNAseq were performed on A52 cells from both cell culture and syngeneic tumor tissue, as well as a reference cell line representing non-tumor cells, AML-12.

RESULTS

A52 was found to show robust growth in all medium compositions. Substantial chromosomal instability was observed in A52, including trisomy 15 and notable amplifications of oncogenic loci such as Myc and Cd274 (PDL-1), alongside frequent small variants and structural rearrangements. Notably, the cell line harbors the common HCC driver Braf V584E mutation, and a novel Plk1 p.R364W variant predicted as a driver mutation. Transcriptomic profiling defined a distinct "A52 gene signature" enriched in EGFR-ERBB signaling and cell migration pathways. Integrative analyses demonstrated that the A52 gene signature aligns closely with a subset of human HCC lacking CTNNB1 mutations.

CONCLUSION

This study provides a critical genetic resource, facilitating more precise preclinical modeling and therapeutic validation in HCC.