title: Quantitative methylation analysis of HOXA3, 7, 9, and 10 genes in glioma: association with tumor WHO grade and clinical outcome.
abstract: OBJECTIVE
  The purpose of this study was to determine whether specific HOXA epigenetic signatures could differentiate glioma with distinct biological, pathological, and clinical characteristics.
  
  
  METHODS
  We evaluated HOXA3, 7, 9, and 10 methylation in 63 glioma samples by MassARRAY and pyrosequencing.
  
  
  RESULTS
  We demonstrated the direct statistical correlation between the level of methylation of all HOXA genes examined and WHO grading. Moreover, in glioblastoma patients, higher level of HOXA9 and HOXA10 methylation significantly correlated with increased survival probability (HOXA9-HR: 0.36, P = 0.007; HOXA10-HR: 0.46, P = 0.045; combined HOXA9 and 10-HR 0.28, P = 0.004).
  
  
  CONCLUSIONS
  This study identifies HOXA3, 7, 9, and 10 as methylation targets mainly in high-grade glioma and hypermethylation of the HOXA9 and 10 as prognostic factor in glioblastoma patients. Our data indicate that these epigenetic changes may be biomarkers of clinically different subgroups of glioma patients that could eventually benefit from personalized therapeutic strategies.
authors.affiliation: Laboratory of Tumor Genetics and Epigenetics, Istituto Nazionale per la Ricerca sul Cancro, IST Largo Rosanna Benzi 10, 16132, Genoa, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Di Vinci
authors.forename: Ida
authors.initials: I
authors.lastname: Casciano
authors.forename: Elena
authors.initials: E
authors.lastname: Marasco
authors.forename: Barbara
authors.initials: B
authors.lastname: Banelli
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Ravetti
authors.forename: Luana
authors.initials: L
authors.lastname: Borzì
authors.forename: Claudio
authors.initials: C
authors.lastname: Brigati
authors.forename: Alessandra
authors.initials: A
authors.lastname: Forlani
authors.forename: Alessandra
authors.initials: A
authors.lastname: Dorcaratto
authors.forename: Giorgio
authors.initials: G
authors.lastname: Allemanni
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Zona
authors.forename: Renato
authors.initials: R
authors.lastname: Spaziante
authors.forename: Henning
authors.initials: H
authors.lastname: Gohlke
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gardin
authors.forename: Domenico Franco
authors.initials: DF
authors.lastname: Merlo
authors.forename: Vilma
authors.initials: V
authors.lastname: Mantovani
authors.forename: Massimo
authors.initials: M
authors.lastname: Romani
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002897:Chromosomes, Human, Pair 7; D016000:Cluster Analysis; D019175:DNA Methylation; D005784:Gene Amplification; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D060787:Neoplasm Grading; D015996:Survival Rate
chemical_list: C489832:HOXA3 protein, human; C115962:HOXA7 protein, human; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; C097899:homeobox protein HOXA9; C069634:HOXA10 protein, human; C088144:HoxA protein