Molecular characterization of the A52 murine hepatocellular carcinoma cell line
Gillman, Rhys, Sun, Eun Jin, Wankell, Miriam, Field, Matt A., Schmitz, Ulf, and Hebbard, Lionel (2026) Molecular characterization of the A52 murine hepatocellular carcinoma cell line. Animal Models and Experimental Medicine, 9 (3). pp. 546-557.
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Abstract
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.
| Item ID: | 91799 |
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| Item Type: | Article (Research - C1) |
| ISSN: | 2576-2095 |
| Keywords: | carcinoma, cell line, gene expression profiling, genomics, hepatocellular, mice |
| Copyright Information: | © 2026 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Funders: | National Health and Medical Research Council (NHMRC) |
| Projects and Grants: | NHMRC 1196405, NHMRC 5121190 |
| Date Deposited: | 01 Sep 2026 05:03 |
| FoR Codes: | 32 BIOMEDICAL AND CLINICAL SCIENCES > 3211 Oncology and carcinogenesis > 321111 Solid tumours @ 100% |
| SEO Codes: | 20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions @ 100% |
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