Deregulation of Ion Channel and Transporter Encoding Genes in Pediatric Gliomas

Valentina Cetica,Anna Maria Buccoliero,Lorenzo Genitori,Duccio Fanelli,Marika Masselli,Pasquale Laise,Martina Da Ros,Serena Pillozzi,Annarosa Arcangeli,Giulia Tonini,Iacopo Sardi,Andrea Becchetti,Maurizio Aricò

doi:10.3389/fonc.2012.00053

Abstract

Brain tumors, including the majority gliomas, are the leading cause of cancer-related death in children. World Health Organization has divided pediatric brain tumors into different grades and, based upon cDNA microarray data identifying gene expression profiles (GEPs), it has become evident in the last decade that the various grades involve different types of genetic alterations. However, it is not known whether ion channel and transporter genes, intimately involved in brain functioning, are associated with such GEPs. We determined the GEPs in an available cohort of 10 pediatric brain tumors initially by comparing the data obtained from four primary tumor samples and corresponding short-term cultures. The correspondence between the two types of samples was statistically significant. We then performed bioinformatic analyses on those samples (a total of nine) which corresponded to tumors of glial origin, either tissues or cell cultures, depending on the best “RNA integrity number.” We used R software to evaluate the genes which were differentially expressed (DE) in gliomas compared with normal brain. Applying a p-value below 0.01 and fold change ≥4, led to identification of 2284 DE genes. Through a Functional Annotation Analysis (FAA) using the NIH-DAVID software, the DE genes turned out to be associated mainly with: immune/inflammatory response, cell proliferation and survival, cell adhesion and motility, neuronal phenotype, and ion transport. We have shown that GEPs of pediatric brain tumors can be studied using either primary tumor samples or short-term cultures with similar results. From FAA, we concluded that, among DE genes, pediatric gliomas show a strong deregulation of genes related to ion channels and transporters.

Highlights

Brain tumors are the most common solid malignancy and the leading cause of cancer-related deaths in children (Pollack et al, 2006; Dubuc et al, 2010)
We determined the gene expression profiles (GEPs) in an available cohort of 10 pediatric brain tumors initially by comparing the data obtained from four primary tumor samples and corresponding short-term cultures
We have shown that GEPs of pediatric brain tumors can be studied using either primary tumor samples or short-term cultures with similar results

Summary

Introduction

Brain tumors are the most common solid malignancy and the leading cause of cancer-related deaths in children (Pollack et al, 2006; Dubuc et al, 2010). Among these cancers, gliomas represent the vast majority, ranging from 56 to 70%, depending on the registry and the histological criteria used (Qaddoumi et al, 2009). The most common pediatric gliomas are astrocytomas and ependymomas They are classified as low grade gliomas (LGGs) and high grade gliomas (HGGs; Qaddoumi et al, 2009). Despite aggressive surgical resection and radiotherapy accompanied or followed by adjuvant chemotherapy, pHGGs prognosis remains poor (Massimino et al, 2010)

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