IDENTIFICATION OF SMARC DEFICIENT PEDIATRIC TUMORS FOR DRUG SCREENING/TESTING

Mayara Ferreira Euzébio; Felipe Luz Torres Silva; Iva Loureiro Hoffmann; Camila Maia Martin Daiggi; Izilda Aparecida Cardinalli; Helder Tedeschi; Ana Luiza Seidinger; Patricia Yoshioka Jotta; Mariana Maschietto

Todos os Trabalhos

Trabalho

Título do Trabalho

IDENTIFICATION OF SMARC DEFICIENT PEDIATRIC TUMORS FOR DRUG SCREENING/TESTING

Autores

Mayara Ferreira Euzébio
Felipe Luz Torres Silva
Iva Loureiro Hoffmann
Camila Maia Martin Daiggi
Izilda Aparecida Cardinalli
Helder Tedeschi
Ana Luiza Seidinger
Patricia Yoshioka Jotta
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/609741-identification-of-smarc-deficient-pediatric-tumors-for-drug-screeningtesting

ISBN

978-85-5722-785-9

Palavras-Chave

pediatric cancers, molecular markers , methylation profiles , copy number alterations, SMARC

Resumo

Identification of SMARC deficient pediatric tumors for drug screening/testing Mayara Ferreira Euzébio1,2, Felipe Luz Torres Silva1,2, Iva Loureiro Hoffmann3, Camila Maia Martin Daiggi3, , Izilda Aparecida Cardinalli3, Helder Tedeschi3, Ana Luiza Seidinger1,2, Patricia Y. Jotta1,2, Mariana Maschietto1,2 1 Epigenomics Lab, Research Center, Boldrini Children’s Hospital 2 Graduate Program in Genetics and Molecular Biology - Institute of Biology, State University of Campinas (UNICAMP), Campinas, SP, Brazil. 3 Boldrini Children’s Hospital, Campinas, São Paulo, Brazil. Among pediatric cancers, solid tumors accounts for approximately with 70% 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 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. Here, we evaluated a cohort of 242 pediatric solid tumors from individuals treated at a reference hospital in Brazil. Bisulfite-converted DNA was hybridized 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 copy 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. Deletions in genes from the SMARC family are associated poor prognosis for the patients. They are more commonly reported in high-risk tumors, such as atypical teratoid rhabdoid tumor and rhabdomyosarcomas. We found that 17.4% (42/242) of tumors have at least one SMARC deletion. While we found the more common classes of SMARC deficient tumors, other reported rarer cases, such as osteosarcomas, neuroblastomas, medulloblastomas, ependymomas and others. Primary cells from tumors that were biobanked will be treated with drugs that interfere with this molecular alteration, independent of type tumor. Financial Support: - CAPES; PRONON SIPAR 25000211368/2019-41

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

EUZÉBIO, Mayara Ferreira et al.. IDENTIFICATION OF SMARC DEFICIENT PEDIATRIC TUMORS FOR DRUG SCREENING/TESTING.. 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/609741-IDENTIFICATION-OF-SMARC-DEFICIENT-PEDIATRIC-TUMORS-FOR-DRUG-SCREENINGTESTING. Acesso em: 26/12/2024