Multiplexed methylation profiles of tumor suppressor genes and clinical outcome in oligodendroglial tumors

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• 作者：Lu-Ting Kuo ; Hsueh-Yi Lu ; Chien-Chang Lee ; Jui-Chang Tsai ; Hong-Shiee Lai ; Ham-Min Tseng ; Meng-Fai Kuo and Yong-Kwang Tu
• 刊名：Cancer Medicine
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：5
• 期：8
• 页码：1830-1839
• 全文大小：242K
• ISSN：2045-7634

文摘

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.