Open AccessMultiplexed methylation profiles of tumor suppressor genes and clinical outcome in oligodendroglial tumors
Author(s) -
Kuo LuTing,
Lu HsuehYi,
Lee ChienChang,
Tsai JuiChang,
Lai HongShiee,
Tseng HamMin,
Kuo MengFai,
Tu YongKwang
Publication year - 2016
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.762
Subject(s) - methylation , dna methylation , carcinogenesis , epigenetics , biology , cancer research , tumor progression , survival analysis , multiplex ligation dependent probe amplification , cancer , gene , medicine , genetics , gene expression , exon
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 RASSF 1A (80.3%), CASP 8 (70.5%), and CDKN 2A (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 ESR 1 promoter is significantly associated with shorter duration of overall survival and progression‐free survival, and that methylation of IGSF 4 and RASSF 1A is significantly associated with shorter duration of progression‐free survival. However, none of the methylation status of ESR 1, IGSF 4, and RASSF 1A 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.