Homo sapiens Exome

Hepatoblastoma (HB) is the most common primary liver tumor in children. Mutations in the ß-catenin gene that leads to constitutive activation of Wnt pathway have been detected in a large proportion of HB tumors. To identify novel mutations in HB, we performed whole-exome sequencing of 6 paired HB tumors and their corresponding lymphocytes. This identified 24 somatic non-synonymous mutations in 21 genes, many of which were novel, including three novel mutations targeting the CTNNB1 (G512V) and CAPRIN2 (R968H/S969C) genes in the Wnt pathway, and genes previously shown to be involved in the ubiquitin ligase complex (SPOP, KLHL22, TRPC4AP and RNF169). Functionally, both the CTNNB1 (G512V) and CAPRIN2 (R968H/S969C) were observed to be gain-of-functional mutations in HB. These results extend the landscape of genetic alterations in HB and highlight the dysregulation of Wnt and ubiquitin pathways in HB tumorigenesis.