Patient-Derived Mutant Forms of NFE2L2/NRF2 Drive Aggressive Murine Hepatoblastomas
Huabo Wang, Jie Lu, Jordan A. Mandel, Weiqi Zhang, Marie Schwalbe, Joanna E. Gorka, Ying Liu, Brady Marburger, Jinglin Wang, Sarangarajan Ranganathan, Edward V. Prochownik
Abstract
BACKGROUND & AIMS: . Some HBs and other cancers also express mutants of NFE2L2/NRF2 (NFE2L2), a transcription factor that tempers oxidative and electrophilic stress. In doing so, NFE2L2 either suppresses or facilitates tumorigenesis. METHODS: , and the patient-derived NFE2L2 mutants L30P and R34P in murine livers. We evaluated growth, biochemical and metabolic profiles, and transcriptomes of the ensuing tumors. RESULTS: -L30P/R34P tumors. CONCLUSIONS: Our findings establish the direct oncogenicity of NFE2L2 mutants and key transcripts, including serpin E1, that drive specific HB features.