Characterization of telomere and associated genes in pediatric osteosarcomas

• Grant number: 23/10527-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2024
• End date: February 01, 2026
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Mariana Camargo Maschietto
• Grantee: Ester Fernandes Martins Rodrigues
• Host Institution: Centro Infantil de Investigações Hematológicas Dr Domingos A Boldrini (CIB). Campinas , SP, Brazil
• Associated research grant: 21/06782-7 - Striking the evolutionary process of bone tumors, AP.JP2
• Associated scholarship(s): 25/06104-0 - Characterization of the role of ZFHX4 in osteosarcoma cell lines, BE.EP.IC

Abstract

Pediatric osteosarcomas present several molecular alterations and complex karyotypes, which can be associated with telomere dysfunction. The telomere consists of a repetitive sequence of nucleotides located at the end of chromosomes; it has a role of chromosomal structural integrity maintenance. Two pathways are involved with telomere integrity: the canonical pathway that involves TERT, and the ALT pathway, associated with an alternative telomere elongation mechanism. To proliferate, tumor cells can reactivate the expression of several genes involved with telomere maintenance. Our objective is to evaluate the relationship between telomeres and tumor behavior. Using data from the literature, genes belonging to either telomere maintenance pathways will be evaluated for the presence of mutations. The samples will be divided into two groups: with and without mutations in telomere maintenance pathways. Using transcriptome data and a pipeline previously implemented our the lab, differentially expressed genes between these two groups will be identified for further functional characterization (cellular pathway and ontology enrichment). In these same samples, telomere length will be characterized. The molecular data will then be compared with tumor and patient characteristics.