Genetic and epigenetic anomalies in the childhood tumor hepatoblastoma

Abstract

During embryonic development, an anomalous signal may result in modifications or impairment of cell differentiation and maturation. Such molecular failures during morphogenesis may be points of initiation of childhood tumors, defined as tumors originating in the primary cells that have suffered genetic mutations. Hepatoblastoma (HB) is the most common liver cancer in children and adolescents, consisting of a solid embryonal tumor that presents in most cases high mortality and rapid progression. Hepatoblastomas have very heterogeneous morphology, which recapitulates the various stages of differentiation of the liver. Molecular data for the development of HBs are still rare. In this project we will evaluate three fundamental aspects for the correlation between genotyping and phenotyping in cancer: (1) gains and losses of genetic segments (Somatic Copy Number Alterations - SCNA) to be identified by comparative genomic hybridization in microarrays platform 180K (array-CGH); (2) analysis of gene mutations in coding regions of the genome by sequencing the exome (exome next-generation sequencing), and (3) changes in the pattern of methylation of DNA sequences distributed throughout the genome (genome wide methylation analysis) detected by using Illumina 450K BeadArrays. These tests will be performed in paired samples of hepatoblastomas and normal liver tissue to identify somatic mutations that are involved in carcinogenesis. Our hypothesis is that the identification of genetic pathways involved in hepatoblastoma may contribute to a better understanding of the disruption of normal differentiation of the liver and subsequent development of the carcinogenic process. (AU)