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Integrating multi-omics methodologies to unveil the molecular landscape of bone sarcomas

Grant number: 23/12984-7
Support Opportunities:Scholarships abroad - Research Internship - Doctorate (Direct)
Effective date (Start): December 05, 2023
Effective date (End): November 04, 2024
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Mariana Camargo Maschietto
Grantee:Felipe Luz Torres Silva
Supervisor: Sam Behjati
Host Institution: Centro Infantil de Investigações Hematológicas Dr Domingos A Boldrini (CIB). Campinas , SP, Brazil
Research place: Wellcome Sanger Institute (WSI), England  
Associated to the scholarship:22/04781-6 - Search for the molecular mechanisms involved with the tumorigenesis of bone tumors, BP.DD

Abstract

Bone tumors include osteosarcomas (50%), Ewing sarcomas (40%) and other rarer tumors, all presenting high rates of morbidity and mortality. The methylation profiles enabled the identification of molecular classes of bone sarcomas for which ongoing cohort studies are attempting to correlate with tumor's characteristics and patient's outcome. Each histology presents a typical molecular profile: for example, Ewing sarcomas have structural rearrangements involving EWS and FLI1 or ERG family genes, Ewing-like sarcomas carry rearrangements involving CIC or BCOR and osteosarcomas have a high mutational burden with few recurrently mutated genes. Both DNA methylation and mutation (including chromosomal rearrangements) interfere with the cell transcriptome and are required for cell transformation. Identification of pathways that are common and specific for each bone sarcoma type will point to the cell of origin, which are not known for these sarcomas. The aim of this study is to unveil the molecular alterations underlying bone tumors progression by analyzing DNA methylome, whole exome and transcriptome sequencing as well as by integrating data from the multi-omics methodologies. (AU)

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