title: High-throughput microRNA profiling of pediatric high-grade gliomas.
abstract: BACKGROUND
  High-grade gliomas (HGGs) account for 15% of all pediatric brain tumors and are a leading cause of cancer-related mortality and morbidity. Pediatric HGGs (pHGGs) are histologically indistinguishable from their counterpart in adulthood. However, recent investigations indicate that differences occur at the molecular level, thus suggesting that the molecular path to gliomagenesis in childhood is distinct from that of adults. MicroRNAs (miRNAs) have been identified as key molecules in gene expression regulation, both in development and in cancer. miRNAs have been investigated in adult high-grade gliomas (aHGGs), but scant information is available for pHGGs.
  
  
  METHODS
  We explored the differences in microRNAs between pHGG and aHGG, in both fresh-frozen and paraffin-embedded tissue, by high-throughput miRNA profiling. We also evaluated the biological effects of miR-17-92 cluster silencing on a pHGG cell line.
  
  
  RESULTS
  Comparison of miRNA expression patterns in formalin versus frozen specimens resulted in high correlation between both types of samples. The analysis of miRNA profiling revealed a specific microRNA pattern in pHGG with an overexpression and a proliferative role of the miR-17-92 cluster. Moreover, we highlighted a possible quenching function of miR-17-92 cluster on its target gene PTEN, together with an activation of tumorigenic signaling such as sonic hedgehog in pHGG.
  
  
  CONCLUSIONS
  Our results suggest that microRNA profiling represents a tool to distinguishing pediatric from adult HGG and that miR-17-92 cluster sustains pHGG.
authors.affiliation: Corresponding author: Elisabetta Ferretti, MD, PhD, Department of Experimental Medicine, Sapienza University, Rome, Italy. Viale Regina Elena, 291 - 00161 Rome, Italy. elisabetta.ferretti@uniroma1.it.
authors.forename: Evelina
authors.initials: E
authors.lastname: Miele
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Buttarelli
authors.forename: Antonella
authors.initials: A
authors.lastname: Arcella
authors.forename: Federica
authors.initials: F
authors.lastname: Begalli
authors.forename: Neha
authors.initials: N
authors.lastname: Garg
authors.forename: Marianna
authors.initials: M
authors.lastname: Silvano
authors.forename: Agnese
authors.initials: A
authors.lastname: Po
authors.forename: Caterina
authors.initials: C
authors.lastname: Baldi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Carissimo
authors.forename: Manila
authors.initials: M
authors.lastname: Antonelli
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Spinelli
authors.forename: Carlo
authors.initials: C
authors.lastname: Capalbo
authors.forename: Vittoria
authors.initials: V
authors.lastname: Donofrio
authors.forename: Isabella
authors.initials: I
authors.lastname: Morra
authors.forename: Paolo
authors.initials: P
authors.lastname: Nozza
authors.forename: Alberto
authors.initials: A
authors.lastname: Gulino
authors.forename: Felice
authors.initials: F
authors.lastname: Giangaspero
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ferretti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: C568997:MIR17HG, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D012333:RNA, Messenger
keywords: cancer; expression profiling; microRNA; pediatric gliomas