Abstract
BackgroundPilocytic astrocytoma is the most common type of brain tumor in the pediatric population, with a generally favorable prognosis, although recurrences or leptomeningeal dissemination are sometimes also observed. For tumors originating in the supra-or infratentorial location, a different molecular background was suggested, but plausible correlations between the transcriptional profile and radiological features and/or clinical course are still undefined. The purpose of this study was to identify gene expression profiles related to the most frequent locations of this tumor, subtypes based on various radiological features, and the clinical pattern of the disease.MethodsEighty six children (55 males and 31 females) with histologically verified pilocytic astrocytoma were included in this study. Their age at the time of diagnosis ranged from fourteen months to seventeen years, with a mean age of seven years. There were 40 cerebellar, 23 optic tract/hypothalamic, 21 cerebral hemispheric, and two brainstem tumors. According to the radiological features presented on MRI, all cases were divided into four subtypes: cystic tumor with a non-enhancing cyst wall; cystic tumor with an enhancing cyst wall; solid tumor with central necrosis; and solid or mainly solid tumor. In 81 cases primary surgical resection was the only and curative treatment, and in five cases progression of the disease was observed. In 47 cases the analysis was done by using high density oligonucleotide microarrays (Affymetrix HG-U133 Plus 2.0) with subsequent bioinformatic analyses and confirmation of the results by independent RT-qPCR (on 39 samples).ResultsBioinformatic analyses showed that the gene expression profile of pilocytic astrocytoma is highly dependent on the tumor location. The most prominent differences were noted for IRX2, PAX3, CXCL14, LHX2, SIX6, CNTN1 and SIX1 genes expression even within different compartments of the supratentorial region. Analysis of the genes potentially associated with radiological features showed much weaker transcriptome differences. Single genes showed association with the tendency to progression.ConclusionsHere we have shown that pilocytic astrocytomas of three different locations can be precisely differentiated on the basis of their gene expression level, but their transcriptional profiles does not strongly reflect the radiological appearance of the tumor or the course of the disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1810-z) contains supplementary material, which is available to authorized users.
Highlights
Pilocytic astrocytoma is the most common type of brain tumor in the pediatric population, with a generally favorable prognosis, recurrences or leptomeningeal dissemination are sometimes observed
An assumption describing different expression profiles for Pilocytic astrocytoma (PA) of various locations was given by Sharma et al, who showed the LHX2 gene expression to be connected with supratentorial location [7]
On the basis of observations made to date we verified the hypothesis that the location of pilocytic astrocytomas is the major cause of their genomic differences, and tried to find genes connected with patient outcome and tumor appearance
Summary
Pilocytic astrocytoma is the most common type of brain tumor in the pediatric population, with a generally favorable prognosis, recurrences or leptomeningeal dissemination are sometimes observed. Pilocytic astrocytoma (PA) is the most common type of brain tumor in the pediatric population, comprising approximately 25 % of all primary tumors, with the most frequent occurrence taking place between 5–10 years of age This tumor has a generally good outcome, recurrences or leptomeningeal dissemination are sometimes observed. MATN2 and ALDH1L1 genes were assumed to be connected with plausible PAs progression despite total surgical resection [9, 10] Children affected by this tumor usually have a good prognosis, in some cases recurrence or leptomeningeal dissemination may be observed [11,12,13,14]. The aim of this study was to identify gene expression profiles related to the most frequent locations, radiological features, and the clinical course of the disease in a representative group of Polish children with PAs
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