title: Multiplexed methylation profiles of tumor suppressor genes and clinical outcome in oligodendroglial tumors.
abstract: Aberrant methylation has been associated with transcriptional inactivation of tumor-related genes in a wide spectrum of human neoplasms. The influence of DNA methylation in oligodendroglial tumors is not fully understood. Genomic DNA was isolated from 61 oligodendroglial tumors for analysis of methylation using methylation-specific multiplex ligation-dependent probe amplification assay (MS-MLPA). We correlated methylation status with clinicopathological findings and outcome. The genes found to be most frequently methylated in oligodendroglial tumors were RASSF1A (80.3%), CASP8 (70.5%), and CDKN2A (52.5%). Kaplan-Meier survival curve analysis demonstrated longer duration of progression-free survival in patients with 19q loss, aged less than 38 years, and with a proliferative index of less than 5%. Methylation of the ESR1 promoter is significantly associated with shorter duration of overall survival and progression-free survival, and that methylation of IGSF4 and RASSF1A is significantly associated with shorter duration of progression-free survival. However, none of the methylation status of ESR1, IGSF4, and RASSF1A was of prognostic value for survival in a multivariate Cox model. A number of novel and interesting epigenetic alterations were identified in this study. The findings highlight the importance of methylation profiles in oligodendroglial tumors and their possible involvement in tumorigenesis.
authors.affiliation: Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan.
authors.forename: Lu-Ting
authors.initials: LT
authors.lastname: Kuo
authors.affiliation: Department of Industrial Engineering and Management, National Yunlin University of Science and Technology, Douliu, Yunlin county, 640, Taiwan.
authors.forename: Hsueh-Yi
authors.initials: HY
authors.lastname: Lu
authors.affiliation: Department of Emergency Medicine, National Taiwan University Hospital, Yun-Lin branch, Yun-Lin county, 640, Taiwan.
authors.forename: Chien-Chang
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan.
authors.forename: Jui-Chang
authors.initials: JC
authors.lastname: Tsai
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Hong-Shiee
authors.initials: HS
authors.lastname: Lai
authors.affiliation: Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan.
authors.forename: Ham-Min
authors.initials: HM
authors.lastname: Tseng
authors.affiliation: Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan.
authors.forename: Meng-Fai
authors.initials: MF
authors.lastname: Kuo
authors.affiliation: Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan.
authors.forename: Yong-Kwang
authors.initials: YK
authors.lastname: Tu
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D049109:Cell Proliferation; D002648:Child; D002869:Chromosome Aberrations; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction / Q000379:methods; D060787:Neoplasm Grading; D009837:Oligodendroglioma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm
keywords: ESR1; IGSF4; methylation; multiplex ligation-dependent probe amplification assay; oligodendroglioma