Establishment and cytogenetic and molecular characterization of two hepatoblastoma cell lines

• Grant number: 18/25506-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2019
• End date: March 31, 2020
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Ana Cristina Victorino Krepischi
• Grantee: Annie Tomoe Takaesu
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Pediatric cancer presents a low incidence when compared to the cancer that develops in adults, presenting great differences regarding its biology and the causes that lead to its emergence, as the smaller involvement of environmental risk factors and short temporal window for its development. Hepatoblastoma is an embryonic liver tumor that develops in the first years of life, with liver cancer being more frequent in childhood. It is characterized by the presence of chromosomal aneuploidies, especially gains of whole chromosomes, and presents the lowest number of somatic mutations among solid tumors. Among the gene alterations associated with this tumor type, there are few genes with recurrent mutations, especially CTNNB1, which cause stability of this protein and activation of the Wnt pathway, in addition to mutations in the TERT gene promoter, which are generally associated with a worse prognosis. Because it is an extremely rare tumor type (approximately 11 cases per million among children under the age of 18 months), there are few studies with hepatoblastoma samples, with most of the work being done on a single commercially available line (HEPG2). This study aims at the establishment and characterization of two cell lines of hepatoblastomas derived from tumors of different patients, aiming their use in future studies. The characterization of these lines will be carried out cytogenetically, by karyotype and genomic microarray analysis to identify chromosomal alterations, as well as the study of somatic mutations by Sanger sequencing (CTNNB1 and TERT genes) and exoma.