Banca de DEFESA: MARCEL DA CÂMARA RIBEIRO DANTAS

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
DISCENTE : MARCEL DA CÂMARA RIBEIRO DANTAS
DATA : 21/09/2018
HORA: 14:00
LOCAL: BioME
TÍTULO:

Reverse engineering of Ewing Sarcoma regulatory network uncovers PAX7 and RUNX3 as master regulators associated with good prognosis.

PALAVRAS-CHAVES:

Pediatric cancer. Transcription Factor. Systems biology. Cancer of unknown primary. Regulome.

PÁGINAS: 41
GRANDE ÁREA: Ciências Biológicas
ÁREA: Biologia Geral
RESUMO:

Ewing Sarcoma (ES) is a rare malignant bone tumor with high propensity to metastasize occurring most frequently in adolescents and young adults. There is no ES cell of origin identified só far and the hallmark of this cancer is the occurrence of a chromosomal translocation between the chromosomes 11 and 22 that results in an aberrant transcription factor through the fusion of a gene from FET family and ETS family, commonly EWSR1 and FLI1. The translocation is associated with chromatin alteration, leading to a significant disturbance in the cell transcriptome. The regulatory mechanisms behind the observed ES transcriptional alterations remain poorly understood. Here, we inferred the transcriptional regulatory network of Ewing Sarcoma and identified 7 transcription factors as potential master regulators. According to our results, these 7 master regulators are organized in two clusters: one composed by PAX7 and RUNX3 and other composed by ARNT2, CREB3L1, GLI3, MEF2C, and PBX3. The master regulators inside each cluster are agonists among each other andboth clusters show antagonism between them. Based on transcriptional data, we classified ES patients of two cohorts according to the activity of each of the seven regulons. High regulatory activity of PAX7 and RUNX3 is associated with better overall survival and high regulatory activity of ARNT2, CREB3L1, GLI3, and PBX3 is associated with worse overall survival. This work contributes to a better understanding of the regulome of Ewing Sarcoma, indicating putative master regulators that can lead to potential prognosis prediction and key factors of tumorigenesis.

MEMBROS DA BANCA:
Presidente - 1507794 - RODRIGO JULIANI SIQUEIRA DALMOLIN
Interno - 2276280 - CESAR RENNO COSTA
Externo à Instituição - MATHEUS AUGUSTO DE BITTENCOURT PASQUALI - UFCG