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

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Darrigo Junior, Luiz Guilherme ^[1] ; Peixoto Lira, Regia Caroline ^[2] ; Fedatto, Paola Fernanda ^[1] ; Marco Antonio, David Santos ^[3] ; Valera, Elvis Terci ^[1] ; Aguiar, Simone ^[4] ; Yunes, Jose Andres ^{[4, 5]} ; Brandalise, Silvia Regina ^[5] ; Neder, Luciano ^[6] ; Saggioro, Fabiano Pinto ^[6] ; Becker, Aline Paixao ^[6] ; de Oliveira, Ricardo Santos ^[7] ; Machado, Helio Rubens ^[7] ; Panepucci, Rodrigo Alexandre ^[8] ; Tone, Luiz Gonzaga ^[1] ; Scrideli, Carlos Alberto ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pediat, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Ctr Univ CESMAC, Maceio, AL - Brazil

^[3] Fleury Grp, Dept Res & Dev, Sao Paulo, SP - Brazil

^[4] Univ Estadual Campinas, Campinas, SP - Brazil

^[5] Boldrinis Children Ctr, Campinas, SP - Brazil

^[6] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pathol, Ribeirao Preto, SP - Brazil

^[7] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Surg, Ribeirao Preto, SP - Brazil

^[8] Univ Sao Paulo, Ribeirao Preto Med Sch, Hemoctr Fdn, Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF NEURO-ONCOLOGY; v. 141, n. 2, p. 373-382, JAN 2019.
• Citações Web of Science: 3

Resumo

PurposesPilocytic 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.MethodsIn 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.ResultsUnsupervised 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.ConclusionsIn summary, our data demonstrate that PA harbors at least two distinct miRNA signatures, including a subgroup of patients with NF1/PA lesions. (AU)

• Processo FAPESP: 10/07020-9 - Estudos moleculares em neoplasias da criança e do adolescente: assinatura de microRNAs e estudos funcionais de genes candidatos a terapia alvo
• Beneficiário: Carlos Alberto Scrideli
• Modalidade de apoio: Auxílio à Pesquisa - Regular