Banca de QUALIFICAÇÃO: MARCEL DA CÂMARA RIBEIRO DANTAS

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
DISCENTE : MARCEL DA CÂMARA RIBEIRO DANTAS
DATA : 03/09/2018
HORA: 14:30
LOCAL: BioME
TÍTULO:

Reverse engineering of ewing sarcoma regulatory network and inference of master regulators

PALAVRAS-CHAVES:

Pediatric cancer. Bioinformatics. Systems biology. Cancer of unknown primary.

PÁGINAS: 21
GRANDE ÁREA: Ciências Biológicas
ÁREA: Biologia Geral
RESUMO:

Ewing Sarcoma (ES) is the second most common malignant bone tumor in adolescents and young adults with high propensity to metastasize due to its aggressive behavior. Studies have showed a five year disease-specific survival rate of around 60%.  There is no ES cell of origin identified so 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 the FET family (EWSR1, usually) and a gene of the ETS family (FLI1, usually). That translocation is associated with chromatin alteration, leading to a significant disturbance in the cell regulome. The regulatory mechanisms behind the observed ES transcriptional alterations remain poorly understood. 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 agonist among each other and both clusters show antagonism between each other. Based in 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 correlates with  better overall survival and high regulatory activity of ARNT2, CREB3L1, GLI3, and PBX3 correlates 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