MicroRNA profile of pediatric pilocytic astrocytomas identifies two tumor-specific signatures when compared to non-neoplastic white matter

  • Luiz Guilherme Darrigo Júnior
  • Regia Caroline Peixoto Lira
  • Paola Fernanda Fedatto
  • David Santos Marco Antonio
  • Elvis Terci Valera
  • Simone Aguiar
  • José Andres Yunes
  • Silvia Regina Brandalise
  • Luciano Neder
  • Fabiano Pinto Saggioro
  • Aline Paixão Becker
  • Ricardo Santos de Oliveira
  • Hélio Rubens Machado
  • Rodrigo Alexandre Panepucci
  • Luiz Gonzaga Tone
  • Carlos Alberto ScrideliEmail author
Clinical Study



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.


Pilocytic 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.

Supplementary material

11060_2018_3042_MOESM1_ESM.docx (18 kb)
Supplementary material 1 (DOCX 17 KB)


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pediatrics, Ribeirão Preto Medical SchoolUniversity of Sao Paulo - USPRibeirão PretoBrazil
  2. 2.Centro Universitário CESMACMaceióBrazil
  3. 3.Department of Research and DevelopmentFleury GroupSão PauloBrazil
  4. 4.State University of CampinasCampinasBrazil
  5. 5.Boldrini´s Children CenterCampinasBrazil
  6. 6.Department of Pathology, Ribeirão Preto Medical SchoolUniversity of Sao PauloRibeirão PretoBrazil
  7. 7.Department of Surgery, Ribeirão Preto Medical SchoolUniversity of Sao PauloRibeirão PretoBrazil
  8. 8.Hemocentro Foundation, Ribeirão Preto Medical SchoolUniversity of Sao PauloRibeirão PretoBrazil

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