Dados do Trabalho


Identification of SMARC deficient pediatric tumors for drug screening/testing


Among pediatric cancers, solid tumors accounts for approximately with 30% of cases. Central nervous system (CNS) tumors are the second most frequent type (15%) and the first cause of death. Others solid tumors are distributed among neuroblastoma (6%), Wilms tumor (5%), non-Hodgkin lymphoma (4%), rhabdomyosarcoma (3%), retinoblastoma (3%), osteosarcoma (3%), Ewing’s sarcoma (1%), germ cell tumors (5%), hepatoblastoma and others. Cure rate is ca reach 90% in ideal conditions, but it is the first cause of death by disease worldwide, including in Brazil. For the survivors, patients are at high risk of long-term toxicity and treatment-associated comorbidities that impact their quality of life. The incorporation of molecular markers in tumor diagnosis has improved risk stratification, which impacts on patient prognosis. The World Health Organization already adopted the methylation profiles as the gold standard method for classification of CNS tumors, as methylomes allow to refine their classification, impacting the clinical management and opening the possibility of alternative treatments.


The study aims to perform drug testing in pediatric solid tumors SMARC deficient, previously identified by molecular classification based on methylation profiles .


Here, we evaluated a cohort of 414 pediatric solid tumors from individuals treated at a reference hospital in Brazil. Bisulfite-converted DNA was hybridised in the Illumina MethylationEPIC BeadChip arrays. Methylation profiles were classified in molecular entities using the DKFZ/Heidelberg CNS/sarcoma tumor package (v12.5), and the copu number alterations (CNAs) were characterized.


Similar to other studies, CNS samples were classified with high-confidence classifier score (>0.84) in 80.8% of the cases. For sarcomas, 63.9% of samples were classified with high-confidence classifier score, and others embryonal tumor, the percentage was 77.7%. CNA was used to identify deletions in SMARCA1, SMARCA2, SMARCA4, SMARCA5 and SMARCB1. We found that 10.14% (42/414) of tumors have at least one SMARC deletion. While we found the more common classes of SMARC dificient tumors, other reported rarer cases, such as osteosarcomas, neuroblastomas, medulloblastomas, ependymomas and others.


Once this study are ongoing, primary cells from tumors that were biobanked will be treated with drugs that interfere with this molecular alteration, independent of type tumor.


Methylation profile, pediatric CNS tumors, smarc-deficient tumors

Financiador do resumo

PRONON SIPAR 25.000.069610/2015-43 PRONON
SIPAR 25000211368/2019-41 e 25000.012259/2019-42


Estudo Clínico - Tumores Pediátricos