title: DNA methylation alterations in grade II- and anaplastic pleomorphic xanthoastrocytoma.
abstract: BACKGROUND
  Pleomorphic xanthoastrocytoma (PXA) is a rare WHO grade II tumor accounting for less than 1% of all astrocytomas. Malignant transformation into PXA with anaplastic features, is unusual and correlates with poorer outcome of the patients.
  
  
  METHODS
  Using a DNA methylation custom array, we have quantified the DNA methylation level on the promoter sequence of 807 cancer-related genes of WHO grade II (n = 11) and III PXA (n = 2) and compared to normal brain tissue (n = 10) and glioblastoma (n = 87) samples. DNA methylation levels were further confirmed on independent samples by pyrosequencing of the promoter sequences.
  
  
  RESULTS
  Increasing DNA promoter hypermethylation events were observed in anaplastic PXA as compared with grade II samples. We further validated differential hypermethylation of CD81, HCK, HOXA5, ASCL2 and TES on anaplastic PXA and grade II tumors. Moreover, these epigenetic alterations overlap those described in glioblastoma patients, suggesting common mechanisms of tumorigenesis.
  
  
  CONCLUSIONS
  Even taking into consideration the small size of our patient populations, our data strongly suggest that epigenome-wide profiling of PXA is a valuable tool to identify methylated genes, which may play a role in the malignant progression of PXA. These methylation alterations may provide useful biomarkers for decision-making in those patients with low-grade PXA displaying a high risk of malignant transformation.
authors.affiliation: Department of Neurosurgery, University of Goettingen, Robert Koch, Str, 40, 37075 Goettingen, Germany. ramon.martinez@med.uni-goettingen.de.
authors.forename: Ramón
authors.initials: R
authors.lastname: Martínez
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Carmona
authors.forename: Miguel
authors.initials: M
authors.lastname: Vizoso
authors.forename: Veit
authors.initials: V
authors.lastname: Rohde
authors.forename: Matthias
authors.initials: M
authors.lastname: Kirsch
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schackert
authors.forename: Santiago
authors.initials: S
authors.lastname: Ropero
authors.forename: Werner
authors.initials: W
authors.lastname: Paulus
authors.forename: Alonso
authors.initials: A
authors.lastname: Barrantes
authors.forename: Antonio
authors.initials: A
authors.lastname: Gomez
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000032:analysis*; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D051572:Proto-Oncogene Proteins c-hck / Q000235:genetics; D016601:RNA-Binding Proteins; D017422:Sequence Analysis, DNA; D060225:Tetraspanin 28 / Q000235:genetics; D055815:Young Adult
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D051572:Proto-Oncogene Proteins c-hck; D016601:RNA-Binding Proteins; D060225:Tetraspanin 28; C065501:ASCL2 protein, human; C554798:CD81 protein, human; C489213:HOXA5 protein, human; C429688:TES protein, human; C496631:HCK protein, human