title: ADAR2 editing activity in newly diagnosed versus relapsed pediatric high-grade astrocytomas.
abstract: BACKGROUND
  High-grade (WHO grade III and IV) astrocytomas are aggressive malignant brain tumors affecting humans with a high risk of recurrence in both children and adults. To date, limited information is available on the genetic and molecular alterations important in the onset and progression of pediatric high-grade astrocytomas and, even less, on the prognostic factors that influence long-term outcome in children with recurrence. A-to-I RNA editing is an essential post-transcriptional mechanism that can alter the nucleotide sequence of several RNAs and is mediated by the ADAR enzymes. ADAR2 editing activity is particularly important in mammalian brain and is impaired in both adult and pediatric high-grade astrocytomas. Moreover, we have recently shown that the recovered ADAR2 activity in high-grade astrocytomas inhibits in vivo tumor growth. The aim of the present study is to investigate whether changes may occur in ADAR2-mediated RNA editing profiles of relapsed high-grade astrocytomas compared to their respective specimens collected at diagnosis, in four pediatric patients.
  
  
  METHODS
  Total RNAs extracted from all tumor samples and controls were tested for RNA editing levels (by direct sequencing on cDNA pools) and for ADAR2 mRNA expression (by qRT-PCR).
  
  
  RESULTS
  A significant loss of ADAR2-editing activity was observed in the newly diagnosed and recurrent astrocytomas in comparison to normal brain. Surprisingly, we found a substantial rescue of ADAR2 editing activity in the relapsed tumor of the only patient showing prolonged survival.
  
  
  CONCLUSIONS
  High-grade astrocytomas display a generalized loss of ADAR2-mediated RNA editing at both diagnosis and relapse. However, a peculiar Case, in complete remission of disease, displayed a total rescue of RNA editing at relapse, intriguingly suggesting ADAR2 activity/expression as a possible marker for long-term survival of patients with high-grade astrocytomas.
authors.affiliation: Laboratory of RNA Editing, Department of Pediatric Haematology/Oncology, Bambino Gesù Children's Hospital, IRCCS, Piazza S, Onofrio 4, Rome 00165, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Tomaselli
authors.forename: Federica
authors.initials: F
authors.lastname: Galeano
authors.forename: Luca
authors.initials: L
authors.lastname: Massimi
authors.forename: Concezio
authors.initials: C
authors.lastname: Di Rocco
authors.forename: Libero
authors.initials: L
authors.lastname: Lauriola
authors.forename: Angela
authors.initials: A
authors.lastname: Mastronuzzi
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Angela
authors.initials: A
authors.lastname: Gallo
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D001254:Astrocytoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D001921:Brain; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000378:metabolism; D017393:RNA Editing; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase