UNCOVERING THE MOLECULAR MECHANISMS UNDERLYING BONE TUMORIGENESIS

Felipe Luz Torres Silva; Patricia Yoshioka Jotta; Mayara Ferreira Euzébio; José Andrés Yunes; Mariana Maschietto

Todos os Trabalhos

Trabalho

Título do Trabalho

UNCOVERING THE MOLECULAR MECHANISMS UNDERLYING BONE TUMORIGENESIS

Autores

Felipe Luz Torres Silva
Patricia Yoshioka Jotta
Mayara Ferreira Euzébio
José Andrés Yunes
Mariana Maschietto

Modalidade

Apresentação de Pôster

Área temática

Genética Animal e Evolução

Data de Publicação

09/06/2023

País da Publicação

Brasil

Idioma da Publicação

Inglês

Página do Trabalho

https://www.even3.com.br/anais/v-gbmeeting/609556-uncovering-the-molecular-mechanisms-underlying-bone-tumorigenesis

ISBN

978-85-5722-785-9

Palavras-Chave

Pediatric cancer, Bone sarcomas, single-cell RNAseq

Resumo

Among the various childhood cancers, those originating from bone tissue account for 4% to 8% of cases and present a high rate of mortality and morbidity. Among them, osteosarcomas and Ewing sarcomas are the most prevalent (50% and 40%, respectively). Osteosarcomas present complex karyotypes, with numerous structural alterations, copy number alterations (CNA), aneuploidies and some gene fusions, such as FAM105B-EIF1, JARID2-WRAP53, TNFRSF1A-RAB10, MAP4K4-GAS2, TET3-MEF2C and USP43-FGD2. Ewing sarcomas are embryonic tumors, which typically have few mutated genes. The main molecular alterations are the structural rearrangements involving the EWS and FLI1 or EWS and ERG families. However, although these translocations are necessary, they are not sufficient for the Ewing sarcomatogenesis. Ewing-like sarcomas include CIC and BCOR -rearranged sarcomas, EWSR1-non-ETS sarcomas and unclassified undifferentiated round cell sarcomas. Transcriptome characterization of tumors is typically based on mixed cell populations and lacks resolution to determine specific cell types to elucidate intratumoral heterogeneity and biology of bone tumors. Single-cell RNA sequencing (sc-RNAseq) could both access this intratumoral heterogeneity as well as the cellular crosstalk with the tumor microenvironment. The main goal of this project is to integrate multiomics analysis, such as methylome, Whole Exome Sequencing (WES) and sc-RNAseq to identify the accumulation of changes, whether epigenetic, structural, mutational or gene expression, necessary to trigger different phenotypes among bone sarcomas. From the 250 pediatric solid tumor methylomes, used for tumor classification, we selected 20 cases that were molecularly classified as osteosarcoma, Ewing sarcoma or Ewing-like sarcoma. Of these, all have a paired WES and will proceed to a sc-RNAseq. So far, we have chracterized the CNAs. Osteosarcomas had chromotripsis events, with MYC amplification and PTEN deletion while Ewing sarcoma presented EGFR and chromosomes 15 and 16 amplifications. Ewing-like sarcomas were reclassified in BCOR and CIC alterated sarcomas, both showing a flat genome, which are in line with the literature. Analysis of WES are undeway to then proceed to 3D cell culture followed by sc-RNAseq.

Título do Evento: V GBMeeting
Cidade do Evento: Campinas
Título dos Anais do Evento: Anais do GBMeeting: Encontro Anual da Pós Graduação em Genética e Biologia Molecular da UNICAMP
Nome da Editora: Even3
Meio de Divulgação: Meio Digital

Como citar

SILVA, Felipe Luz Torres et al.. UNCOVERING THE MOLECULAR MECHANISMS UNDERLYING BONE TUMORIGENESIS.. In: Anais do GBMeeting: Encontro Anual da Pós Graduação em Genética e Biologia Molecular da UNICAMP. Anais...Campinas(SP) Unicamp, 2023. Disponível em: https//www.even3.com.br/anais/v-gbmeeting/609556-UNCOVERING-THE-MOLECULAR-MECHANISMS-UNDERLYING-BONE-TUMORIGENESIS. Acesso em: 17/05/2025