Hepatoblastoma (HB) is the most common pediatric liver cancer and can be classified into several different types. In mice, HBs can be generated by overexpressing in their livers any pairwise or triple combination of three genes that are commonly deregulated in human HBs: ?-catenin (B), YAP (Y) and NRF2 (N). The 4 resulting tumor types (BY, BN, YN and BYN) share many features with human tumors and are currently the best animal surrogates for human HB. Unfortunately, we are hampered by a lack of established HB cell lines from either humans or mice that could otherwise facilitate many critical studies. We have recently discovered that immortalized HB cell lines can be easily established from primary murine HBs by concurrently inactivating gene known as Cdkn2a that normally functions to suppress the growth of many tumor types, including HB. Thus far, 8 BY, 3 BYN, 1 BN and 1 YN cell line have been generated and 12 can be re-grown as under the skin or in the lungs. Moreover, under certain conditionsthese cell lines appear to be able to assume the appearance and function of blood vessel-forming cells known as endothelial cells that are known to facilitate tumor growth by of providing a source of oxygen and nutrients necessary for growth. Molecularly defined HB cell lines will allow us to address several important questions. These include whether tumors generated by different combinations of driver oncogenes utilize similar molecular strategies to generate endothelial cells.