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Search for the molecular mechanisms involved with the tumorigenesis of bone tumors

Grant number: 22/04781-6
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): July 01, 2022
Effective date (End): December 31, 2024
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Mariana Camargo Maschietto
Grantee:Felipe Luz Torres Silva
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


Malignant tumors originating from bone tissue represent between 4% and 8% of childhood cancers, with Osteosarcoma (50%) and Ewing's Sarcoma (40%) being the most frequent. Osteosarcomas present several alterations, however few genes are recurrently mutated, such as TP53, RB1, CDKN2A, MYC, TGFB1. About 90% of Ewing Sarcomas present translocations involving the EWSR1 and FLI1/ERG family of genes. Although this change is necessary, it is not sufficient for cell transformation, suggesting that additional molecular changes are necessary. Moreover, intra and intertumoral heterogeneity add a layer of complexity to properly define the cells of origin of these tumors as well as the steps associated with cell transformation. The objective of this work, therefore, is to determine the identity of the cells of origin of Osteosarcoma and Ewing's Sarcoma by characterizing Osteosarcomas and Ewing's Sarcomas at sinlge cell RNAseq as well as the exomes. The results will be evaluated in tissue samples from 40 Osteosarcomas and 30 Ewing Sarcomas that will have both transcriptome and exome characterized. (AU)

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