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The cerebral cortex size controlling gene, ASPM, gene expression in childhood and adolescence brain tumors

Grant number: 17/26902-1
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2018
Effective date (End): December 31, 2018
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Silvia Regina Caminada de Toledo
Grantee:Débora Cabral de Carvalho Corrêa
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Central Nervous System (CNS) tumors in children represent the most common neoplasia of childhood and adolescence. The ability to analyze tissues on a genomic scale modified the understanding of these tumors and allowed the identification of several subgroups. According to the new classification of brain tumors, established by the World Health Organization, the diagnosis is based on the histological classification, the tumor grade, and its molecular characteristics. Among the CNS tumors of childhood and adolescence, neuroepithelial tumors are the most frequent ones, which include gliomas, medulloblastoma and ependymoma. The ASPM gene is responsible for the most common type of autosomal recessive microcephaly. This gene is the major determinant in the cortical cerebral size of primates, including humans, since its function in the expansion of neuronal progenitor cells and its location in the mitotic spindle and centrioles allow the regulation of brain development by mechanisms associated with cell division. Besides its role in embryonic development, the ASPM gene is involved in the growth of several types of tumors, including medulloblastoma and gliomas. The inhibition of the ASPM gene demonstrated a reduction in the number of progenitor cells located in the ventricular zone, leading to the suggestion of an ASPM role in the increase of neural cells. Growth of the cerebellum is typically reduced in primary microcephaly, whereas in medulloblastoma there is an excessive growth of this region. Therefore, the investigation of the ASPM gene in tumors of the central nervous system in children and adolescents can expand the understanding of the mechanisms involved in the tumorigenesis process of these tumors.