MicroRNA profile of pediatric pilocytic astrocytomas identifies two tumor-specific signatures when compared to non-neoplastic white matter
Pilocytic astrocytoma (PA) is a low-grade neoplasm frequently found in childhood. PA is characterized by slow growth and a relatively good prognosis. Genetic mechanisms such as activation of MAPK, BRAF gene deregulation and neurofibromatosis type 1 (NF1) syndrome have been associated with PA development. Epigenetic signature and miRNA expression profile are providing new insights about different types of tumor, including PAs.
In the present study we evaluated global miRNA expression in 16 microdissected pediatric PA specimens, three NF1-associated PAs and 11 cerebral white matter (WM) samples by the microarray method. An additional cohort of 20 PAs was used to validate by qRT-PCR the expression of six miRNAs differentially expressed in the microarray data.
Unsupervised hierarchical clustering analysis distinguished one cluster with nine PAs, including all NF1 cases and a second group consisting of the WM samples and seven PAs. Among 88 differentially expressed miRNAs between PAs and WM samples, the most underexpressed ones regulate classical pathways of tumorigenesis, while the most overexpressed miRNAs are related to pathways such as focal adhesion, P53 signaling pathway and gliomagenesis. The PAs/NF1 presented a subset of underexpressed miRNAs, which was also associated with known deregulated pathways in cancer such as cell cycle and hippo pathway.
In summary, our data demonstrate that PA harbors at least two distinct miRNA signatures, including a subgroup of patients with NF1/PA lesions.
KeywordsPilocytic astrocitoma Neurofibromatosis type 1 miRNA Global expression
This work was supported by the Brazilian Public Research Agencies: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Grant Number: 2010/07020-9; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Grant Number: 471885/2013-4.
Compliance with ethical standards
Conflict of interest
All authors declare that they had no conflict of interest that could be perceived to impair the impartiality of the research reported.
- 1.Gutmann DH, Hedrick NM, Li J et al (2002) Comparative gene expression profile analysis of neurofibromatosis 1-associated and sporadic pilocytic astrocytomas. Cancer Res 62:2085–2091Google Scholar
- 2.Fernandez C, Figarella-Branger D, Girard N et al (2003) Pilocytic astrocytomas in children: prognostic factors—a retrospective study of 80 cases. Neurosurgery 53:544–555. https://doi.org/10.1227/01.NEU.0000079330.01541.6E CrossRefGoogle Scholar
- 7.Bornhorst M, Frappaz D, Packer RJ (2016) Pilocytic astrocytomas. In: Handbook of clinical neurology. Elsevier, Amsterdam, pp 329–344Google Scholar