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Hepatoblastoma Research Update: New Findings Point to Molecular Basis for Aggressive Disease

June 15, 2021

A research team from the laboratory of Edward Prochownik, MD, PhD, in the Division of Pediatric Hematology/Oncology at UPMC Children’s Hospital of Pittsburgh has uncovered how mutations in a gene known as NFE2L2/NRF2, in combination with ß-catenin and YAP mutations drive the genesis of highly aggressive forms of hepatoblastoma, the most common liver malignancy in children. 

The study also identified a key group of 22 genes that are regulated in all forms of hepatoblastoma and whose expression was altered by any combination of ß-catenin, YAP, and NFE2L2/NRF2. The level of expression of a 10 gene subset of these genes was also able to predict with a high degree of accuracy those human patients who were less likely to survive.   

Given that these aggressive forms of hepatoblastoma in pediatric patients are very difficult to treat and have poor survival, the findings of this study will be significant for further exploration of the mechanistic actions of the target genes and their products, and potential therapeutic development targeting these features of aggressive disease variants.

The study1 was published in March in the journal Cellular and Molecular Gastroenterology and Hepatology. Huabo Wang, PhD, was the lead author of the paper. Edward V. Prochownik, MD, PhD, the Paul C. Gaffney Professor of Pediatrics and professor of microbiology and Molecular Genetics, was the senior author of the study.

An editorial on the study's findings and the potential clinical impact was also published in March from Nikolai A Timchenko, PhD, from Cincinnati Children’s Hospital Medical Center.2

Learn more about the Prochownik Laboratory.


1. Wang H, Lu J, Mandel JA, Zhang W, Schwalbe M, Gorka J, Liu Y, Marburger B, Wang J, Ranganathan S, Prochownik EV. Patient-Derived Mutant Forms of NFE2L2/NRF2 Drive Aggressive Murine Hepatoblastomas. Cell Mol Gastroenterol Hepatol. 2021; 12: 199-228.

2. Timchenko NA. Help for Sick Kids: New Insights Into Hepatoblastoma. Editorial. Cell Mol Gastroenterol Hepatol. 26 March 2021.