Transcriptional profiles of pilocytic astrocytoma are related to their three different locations, but not to radiological tumor features.
BACKGROUND
Pilocytic 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.


METHODS
Eighty 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).


RESULTS
Bioinformatic 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.


CONCLUSIONS
Here 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.
Department of Neurosurgery, Polish Mother Memorial Hospital Research Institute, Rzgowska 281/289, 93-338, Lodz, Poland. krzysztof.zakrzewski_xl@wp.pl.
Krzysztof
K
Zakrzewski
Third Department of Radiotherapy and Chemotherapy, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Wybrzeze Armii Krajowej 15, 44-101, Gliwice, Poland. mjarzab@io.gliwice.pl.
Michał
M
Jarząb
Department of Nuclear Medicine and Endocrine Oncology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Wybrzeze Armii Krajowej 15, 44-101, Gliwice, Poland. apfeifer@io.gliwice.pl.
Aleksandra
A
Pfeifer
Department of Nuclear Medicine and Endocrine Oncology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Wybrzeze Armii Krajowej 15, 44-101, Gliwice, Poland. gosiaoczko@io.gliwice.pl.
Małgorzata
M
Oczko-Wojciechowska
Department of Nuclear Medicine and Endocrine Oncology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Wybrzeze Armii Krajowej 15, 44-101, Gliwice, Poland. bjarzab@io.gliwice.pl.
Barbara
B
Jarząb
Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Pomorska 251, 92-213, Lodz, Poland. pawel.liberski@umed.lodz.pl.
Paweł P
PP
Liberski
Department of Molecular Pathology and Neuropathology, Medical University of Lodz, Pomorska 251, 92-213, Lodz, Poland. magdalena.zakrzewska@umed.lodz.pl.
Magdalena
M
Zakrzewska
D000293:Adolescent; D001254:Astrocytoma / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D011859:Radiography; D059467:Transcriptome