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01-01-2019 | Clinical Study

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

Authors: 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 Scrideli

Published in: Journal of Neuro-Oncology | Issue 2/2019

Abstract

Purposes

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.

Methods

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.

Results

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.

Conclusions

In summary, our data demonstrate that PA harbors at least two distinct miRNA signatures, including a subgroup of patients with NF1/PA lesions.

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Gutmann DH, Hedrick NM, Li J et al (2002) Comparative gene expression profile analysis of neurofibromatosis 1-associated and sporadic pilocytic astrocytomas. Cancer Res 62:2085–2091PubMed

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 CrossRefPubMed

Louis D, Carvenee W (2007) WHO classification of tumours of the central nervous system. Acta Neuropathol 114(2):97–109CrossRef

Burkhard C, Di Patre P-L, Schüler D et al (2003) A population-based study of the incidence and survival rates in patients with pilocytic astrocytoma. J Neurosurg 98:1170–1174. https://doi.org/10.3171/jns.2003.98.6.1170 CrossRefPubMed

Ronghe M, Hargrave D, Bartels U et al (2010) Vincristine and carboplatin chemotherapy for unresectable and/or recurrent low-grade astrocytoma of the brainstem. Pediatr Blood Cancer 55:471–477. https://doi.org/10.1002/pbc.22557 CrossRefPubMed

Sawamura Y, Kamoshima Y, Kato T et al (2009) Chemotherapy with cisplatin and vincristine for optic pathway/hypothalamic astrocytoma in young children. Jpn J Clin Oncol 39:277–283. https://doi.org/10.1093/jjco/hyp012 CrossRefPubMed

Bornhorst M, Frappaz D, Packer RJ (2016) Pilocytic astrocytomas. In: Handbook of clinical neurology. Elsevier, Amsterdam, pp 329–344

Bergthold G, Bandopadhayay P, Bi WL et al (2014) Pediatric low-grade gliomas: how modern biology reshapes the clinical field. Biochim Biophys Acta 1845:294–307. https://doi.org/10.1016/j.bbcan.2014.02.004 CrossRefPubMedPubMedCentral

Jones DTW, Gronych J, Lichter P et al (2012) MAPK pathway activation in pilocytic astrocytoma. Cell Mol Life Sci 69:1799–1811. https://doi.org/10.1007/s00018-011-0898-9 CrossRefPubMed

10.

Ho C, Bar E, Giannini C et al (2013) MicroRNA profiling in pediatric pilocytic astrocytoma reveals biologically relevant targets, including PBX3, NFIB, and METAP2. Neuro Oncol 15:69–82CrossRefPubMed

11.

Dahiya S, Yu J, Kaul A et al (2012) Novel BRAF alteration in a sporadic pilocytic astrocytoma. Case Rep Med 2012:418672. https://doi.org/10.1155/2012/418672 CrossRefPubMedPubMedCentral

12.

Kluwe L, Hagel C, Tatagiba M et al (2001) Loss of NF1 alleles distinguish sporadic from NF1-associated pilocytic astrocytomas. J Neuropathol Exp Neurol 60:917–920CrossRefPubMed

13.

Pfister S, Hartmann C, Korshunov A (2009) Histology and molecular pathology of pediatric brain tumors. J Child Neurol 24:1375–1386. https://doi.org/10.1177/0883073809339213 CrossRefPubMed

14.

Catania A, Maira F, Skarmoutsou E et al (2012) Insight into the role of microRNAs in brain tumors (review). Int J Oncol 40:605–624. https://doi.org/10.3892/ijo.2011.1305 CrossRefPubMed

15.

Hummel R, Maurer J, Haier J (2011) MicroRNAs in brain tumors: a new diagnostic and therapeutic perspective? Mol Neurobiol 44:223–234. https://doi.org/10.1007/s12035-011-8197-x CrossRefPubMed

16.

Zhang B, Pan X, Cobb GP, Anderson T (2007) microRNAs as oncogenes and tumor suppressors. Dev Biol 302:1–12. https://doi.org/10.1016/j.ydbio.2006.08.028 CrossRef

17.

Louis DN, Perry A, Reifenberger G et al (2016) The 2016 world health organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131:803–820CrossRefPubMed

18.

Becker AP, Scapulatempo-Neto C, Carloni AC et al (2015) KIAA1549: BRAF gene fusion and FGFR1 hotspot mutations are prognostic factors in pilocytic astrocytomas. J Neuropathol Exp Neurol 74:743–754. https://doi.org/10.1097/NEN.0000000000000213 CrossRefPubMedPubMedCentral

19.

Meyer SU, Kaiser S, Wagner C et al (2012) Profound effect of profiling platform and normalization strategy on detection of differentially expressed microRNAs—a comparative study. PLoS ONE. https://doi.org/10.1371/journal.pone.0038946 CrossRefPubMedPubMedCentral

20.

Vlachos IS, Zagganas K, Paraskevopoulou MD et al (2015) DIANA-miRPath v3.0: deciphering microRNA function with experimental support. Nucleic Acids Res 43:W460–W466. https://doi.org/10.1093/nar/gkv403 CrossRefPubMedPubMedCentral

21.

Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408. https://doi.org/10.1006/meth.2001.1262 CrossRef

22.

Cowland JB, Hother C, Gronbaek K (2008) MicroRNAs and cancer. J Intern Med 263:366–375. https://doi.org/10.1111/j.1365-2796.2008.01926.x CrossRef

23.

Ambros V (2003) MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell 113:673–676CrossRefPubMed

24.

Diwanji TP, Engelman A, Snider JW, Mohindra P (2017) Epidemiology, diagnosis, and optimal management of glioma in adolescents and young adults. Adolesc Health Med Ther 8:99–113. https://doi.org/10.2147/AHMT.S53391 CrossRefPubMedPubMedCentral

25.

Birks DK, Barton VN, Donson AM et al (2011) Survey of MicroRNA expression in pediatric brain tumors. Pediatr Blood Cancer. https://doi.org/10.1002/pbc CrossRefPubMed

26.

Jeyapalan JN, Doctor GT, Jones TA et al (2016) DNA methylation analysis of paediatric low-grade astrocytomas identifies a tumour-specific hypomethylation signature in pilocytic astrocytomas. Acta Neuropathol Commun 4:54. https://doi.org/10.1186/s40478-016-0323-6 CrossRefPubMedPubMedCentral

27.

Jones TA, Jeyapalan JN, Forshew T et al (2015) Molecular analysis of pediatric brain tumors identifies microRNAs in pilocytic astrocytomas that target the MAPK and NF-κB pathways. Acta Neuropathol Commun 3:86. https://doi.org/10.1186/s40478-015-0266-3 CrossRefPubMedPubMedCentral

28.

Hermeking H (2010) The miR-34 family in cancer and apoptosis. Cell Death Differ 17:193–199. https://doi.org/10.1038/cdd.2009.56 CrossRefPubMed

29.

Vogelstein B, Lane D, Levine AJ (2000) Surfing the p53 network. Nature 408:307CrossRef

30.

Ishii N, Sawamura Y, Tada M et al (1998) Absence of p53 gene mutations in a tumor panel representative of pilocytic astrocytoma diversity using a p53 functional assay. Int J Cancer 800:797–800CrossRef

31.

Gao H, Zhao H, Xiang W (2013) Expression level of human miR-34a correlates with glioma grade and prognosis. J Neurooncol 113:221–228. https://doi.org/10.1007/s11060-013-1119-1 CrossRefPubMed

32.

Sadighi Z, Slopis J (2013) Pilocytic astrocytoma: a disease with evolving molecular heterogeneity. J Child Neurol 28:625–632. https://doi.org/10.1177/0883073813476141 CrossRefPubMed

33.

Zha W, Cao L, Shen Y, Huang M (2013) Roles of Mir-144-ZFX pathway in growth regulation of non-small-cell lung cancer. PLoS ONE. https://doi.org/10.1371/journal.pone.0074175 CrossRefPubMedPubMedCentral

34.

Katayama Y, Maeda M, Miyaguchi K et al (2012) Identification of pathogenesis-related microRNAs in hepatocellular carcinoma by expression profiling. Oncol Lett 4:817–823. https://doi.org/10.3892/ol.2012.810 CrossRefPubMedPubMedCentral

35.

Lin L, Zheng Y, Tu Y et al (2015) MicroRNA-144 suppresses tumorigenesis and tumor progression of astrocytoma by targeting EZH2. Hum Pathol 46:971–980. https://doi.org/10.1016/j.humpath.2015.01.023 CrossRefPubMed

36.

Schmitz KJ, Helwig J, Bertram S et al (2011) Differential expression of microRNA-675, microRNA-139-3p and microRNA-335 in benign and malignant adrenocortical tumours. J Clin Pathol 64:529–535. https://doi.org/10.1136/jcp.2010.085621 CrossRefPubMedPubMedCentral

37.

Li R-Y, Chen L-C, Zhang H-Y et al (2013) MiR-139 inhibits Mcl-1 expression and potentiates TMZ-induced apoptosis in glioma. CNS Neurosci Ther 19:477–483. https://doi.org/10.1111/cns.12089 CrossRefPubMedPubMedCentral

Title: MicroRNA profile of pediatric pilocytic astrocytomas identifies two tumor-specific signatures when compared to non-neoplastic white matter
Authors: 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 Scrideli
Publication date: 01-01-2019
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 2/2019
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-018-03042-6

At a glance: The STEP trials

Springer Medicine

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

Abstract

Purposes

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purposes

Methods

Results

Conclusions

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