Abnormal spindle-like microcephaly-associated (ASPM) gene expression in posterior fossa brain tumors of childhood and adolescence

Abstract

Purpose

In neurogenesis, ASPM (abnormal spindle-like microcephaly-associated) gene is expressed mainly in the ventricular zone of posterior fossa and is the major determinant in the cerebral cortex. Besides its role in embryonic development, ASPM overexpression promotes tumor growth, including central nervous system (CNS) tumors. This study aims to investigate ASPM expression levels in most frequent posterior fossa brain tumors of childhood and adolescence: medulloblastoma (MB), ependymoma (EPN), and astrocytoma (AS), correlating them with clinicopathological characteristics and tumor solid portion size.

Methods

Quantitative reverse transcription (qRT-PCR) is used to quantify ASPM mRNA levels in 80 pre-treatment tumor samples: 28 MB, 22 EPN, and 30 AS. The tumor solid portion size was determined by IOP-GRAACC Diagnostic Imaging Center. We correlated these findings with clinicopathological characteristics and tumor solid portion size.

Results

Our results demonstrated that ASPM gene was overexpressed in MB (p = 0.007) and EPN (p = 0.0260) samples. ASPM high expression was significantly associated to MB samples from patients with worse overall survival (p = 0.0123) and death due to disease progression (p = 0.0039). Interestingly, two patients with AS progressed toward higher grade showed ASPM overexpression (p = 0.0046). No correlation was found between the tumor solid portion size and ASPM expression levels in MB (p = 0.1154 and r = − 0.4825) and EPN (p = 0.1108 and r = − 0.3495) samples.

Conclusion

Taking in account that ASPM gene has several functions to support cell proliferation, as mitotic defects and premature differentiation, we suggest that its overexpression, presumably, plays a critical role in disease progression of posterior fossa brain tumors of childhood and adolescence.

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Funding

This work was supported by grants from FAPESP (The State of São Paulo Research Foundation: 2017/26902-1) and IOP-GRAACC/UNIFESP (Grupo de Apoio ao Adolescente e à Criança e com Câncer).

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Correspondence to Silvia Regina Caminada de Toledo.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (Research Ethics Committee—Federal University of São Paulo no. 0525/2018) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Samples from each primary tumor and healthy brain were collected after informed consent was signed by patients/guardians according to the institutional research committee (Research Ethics Committee—Federal University of São Paulo no. 0525/2018). The biological material is acquired via a Biobank of the Pediatric Oncology Institute-GRAACC/UNIFESP (B-053).

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Cabral de Carvalho Corrêa, D., Dias Oliveira, I., Mascaro Cordeiro, B. et al. Abnormal spindle-like microcephaly-associated (ASPM) gene expression in posterior fossa brain tumors of childhood and adolescence. Childs Nerv Syst (2020). https://doi.org/10.1007/s00381-020-04740-1

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Keywords

  • ASPM gene
  • Gene expression
  • Medulloblastoma
  • Ependymoma
  • Astrocytoma
  • Radial glial cells