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

Abstract

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. Quantitative reverse transcription (qRT-PCR) is used to quantify ASPM mRNA levels in 80 pre-treatment tumor samples: 28MB, 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. 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. 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.