Genetics of pediatric hepatoblastoma and hepatocellular carcinoma and their clinical application

Hepatoblastoma (HB) and hepatocellular carcinoma (HCC) are two main primary liver malignant tumors in children arising from hepatocytes. These pediatric tumors are generally considered to be fatal because of their late diagnosis, underlying liver disease, common metastases, and refractoriness to systemic treatments. Earlier diagnosis, identifying precursor conditions, and proper monitoring and treatment of the tumors can significantly improve the survival rate for the patients with these liver malignancies. A number of unique genetic features have been identified in these tumors. These alterations include germ line mutations of certain genes which result in rare genetic disorders predisposing to pediatric HB and HCC, hallmark cytogenetic changes, and the main somatic recurrent mutations described in these tumors. Moreover, comprehensive genetic analysis of these tumors through next generation sequencing (NGS) not only confirmed previous findings of frequent mutation of CTNNB1 and p53 genes in HB and HCC, but also identified genetic alterations in new tumor associated genes. This review aims to provide an overview of genetic changes in these tumors and outlines the prospects of these findings in clinical application including screening, early diagnosis, patient classification, monitoring, prognosis prediction and treatment optimization. With improved recognition and understanding of these genetic alterations, these findings have been applied in the clinical setting at different levels for genetics-based tumor diagnosis, monitoring and paving the way to individualized cancer treatment.