title: LOH 19q indicates shorter disease progression-free interval in low-grade             oligodendrogliomas with EMP3 methylation.
abstract: We previously described a cohort of grade II oligodendroglioma (OII) patients,             in whom the loss of heterozygosity (LOH) 19q was present in the subgroup at a             higher risk of relapse. In this study, we evaluated the CpG methylation of the             putative tumor suppressor epithelial membrane protein 3 (EMP3, 19q13.3) gene promoter             in the same OII cohort, to investigate whether a correlation could be found between             EMP3 cytogenetic and epigenetic loss and higher risk of relapse. Twenty-three             tumor samples from OII patients were collected over a period of 10 years. Seventeen             glioblastoma (GBM) samples (2 of which were relapses) were collected from 15 patients.             The EMP3, O6-methylguanine methyltransferase (MGMT) and cyclooxygenase 2 (COX2)             promoter methylation, evaluated by methylation-specific PCR, and the isocitrate             dehydrogenase 1 (IDH1) mutation, identified by sequencing, were compared between             the OII and GBM histotypes. The EMP3 promoter methylation was correlated with             the analysis of LOH 19q, performed by microsatellite amplification, in OII patients.             Disease progression-free interval was evaluated in the OII patients with the EMP3             methylation with either LOH 19q or conserved chromosome 19 arms. The EMP3 and             MGMT promoter methylation was more frequent in OII than in GBM patients, and the             IDH1 mutation was absent in GBM. The COX2 promoter was unmethylated in both histotypes.             Both LOH+/- 19q OII patients showed EMP3 hypermethylation. Concomitant LOH 19q             and EMP3 gene promoter methylation was observed in the OII patients at a higher             risk of relapse. Our results suggest that a total (cytogenetic and epigenetic)             functional loss of both EMP3 alleles accounts for the reduced disease progression-free             interval in OII patients. Although the small sample size limits the strength of             this study, our results support testing this hypothesis in larger cohorts of patients,             considering the methylation of the EMP3 gene promoter together with LOH 19q as             an indication for treatment with adjuvant therapy ab initio in order to improve             the overall survival of OII patients.
authors.affiliation: Laboratory of Cellular and Molecular Engineering 'S. Cavalcanti', University of Bologna, Cesena, Italy. alice.pasini@unibo.it
authors.forename: Alice
authors.initials: A
authors.lastname: Pasini
authors.forename: Paolo
authors.initials: P
authors.lastname: Iorio
authors.forename: Emanuela
authors.initials: E
authors.lastname: Bianchi
authors.forename: Serenella
authors.initials: S
authors.lastname: Cerasoli
authors.forename: Anna M
authors.initials: AM
authors.lastname: Cremonini
authors.forename: Marina
authors.initials: M
authors.lastname: Faedi
authors.forename: Carlo
authors.initials: C
authors.lastname: Guarnieri
authors.forename: Graziano
authors.initials: G
authors.lastname: Guiducci
authors.forename: Luca
authors.initials: L
authors.lastname: Riccioni
authors.forename: Chiara
authors.initials: C
authors.lastname: Molinari
authors.forename: Claudia
authors.initials: C
authors.lastname: Rengucci
authors.forename: Daniele
authors.initials: D
authors.lastname: Calistri
authors.forename: Emanuele
authors.initials: E
authors.lastname: Giordano
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D018899:CpG Islands; D051546:Cyclooxygenase 2 / Q000235:genetics; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics; D009837:Oligodendroglioma / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: C485157:EMP3 protein, human; D008562:Membrane Glycoproteins; D051546:Cyclooxygenase 2; D015254:DNA Modification Methylases; D019853:O(6)-Methylguanine-DNA Methyltransferase