Progression-Free Survival in Ovarian Cancer Is Reflected in Epigenetic DNA Methylation Profiles

被引：39
作者：
Bauerschlag, Dirk O. [1 ]
Ammerpohl, Ole [3 ]
Braeutigam, Karen [1 ]
Schem, Christian [4 ]
Lin, Qiong [2 ]
Weigel, Marion T. [4 ]
Hilpert, Felix [4 ]
Arnold, Norbert [4 ]
Maass, Nicolai [1 ]
Meinhold-Heerlein, Ivo [1 ]
Wagner, Wolfgang [2 ]
机构：
[1] Rhein Westfal TH Aachen, Univ Med Ctr Aachen, Dept Gynecol, DE-52074 Aachen, Germany
[2] Rhein Westfal TH Aachen, Univ Med Ctr Aachen, Dept Cell Biol, Helmholtz Inst Biomed Engn, DE-52074 Aachen, Germany
[3] Univ Med Ctr Schleswig Holstein, Inst Human Genet, Kiel, Germany
[4] Univ Med Ctr Schleswig Holstein, Dept Gynecol, Kiel, Germany
来源：
ONCOLOGY | 2011年 / 80卷 / 1-2期
关键词：
Ovarian cancer; Methylation; Epigenetic modification; Progression-free interval; Microarray; CPG-ISLAND METHYLATION; PHASE-III TRIAL; 1ST-LINE TREATMENT; INTERGROUP TRIAL; GENE-EXPRESSION; PROMOTER HYPERMETHYLATION; PROSTATE-CANCER; CARBOPLATIN; PACLITAXEL; BREAST;
D O I：
10.1159/000327746
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Objective: Many patients with ovarian cancer disease relapse within 6 months after adjuvant chemotherapy, with a limited prognosis. Epigenetic modifications have been shown to play an important role in tumor development and formation. Therefore, global analysis of DNA methylation patterns might reveal specific CpG sites that correlate with progression-free interval (PFI) after therapy. Methods: Twenty samples of advanced ovarian cancer with a predominantly serous papillary histological subtype were subjected to DNA methylation profiling. Illumina HumanMethylation27 BeadChip technology was used for simultaneous analysis of 27,578 CpG sites in 1 14,000 genes. Results: Differential DNA methylation of various cytosines correlated with PFI. However, this becomes only significant by classification according to PFI with a cutoff of 1 28 months. Longer survival was associated with hypomethylation at specific CpG sites (e. g. GREB1, TGIF and TOB1) and hypermethylation in other genes (e. g. TMCO5, PTPRN and GUCY2C). Gene ontology analysis revealed that differentially methylated genes were significantly overrepresented in the categories telomere organization, mesoderm development and immune regulation. Conclusion: Epigenetic modifications at specific CpG sites correlate with PFI in ovarian cancer. Therefore, such analysis might be of prognostic value. Copyright (C) 2011 S. Karger AG, Basel
引用
收藏
页码：12 / 20
页数：9
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