Progression-free survival in ovarian cancer is reflected in epigenetic DNA methylation profiles

Dirk Bauerschlag; Ole Ammerpohl; Karen Bräutigam; Christian Schem; Qiong Lin; Marion T. Weigel; Felix Hilpert; Norbert Arnold; Nicolai Maass; Ivo Meinhold-Heerlein; Wolfgang Wagner

doi:10.1159/000327746

Progression-free survival in ovarian cancer is reflected in epigenetic DNA methylation profiles

Dirk Bauerschlag, Ole Ammerpohl, Karen Bräutigam, Christian Schem, Qiong Lin, Marion T. Weigel, Felix Hilpert, Norbert Arnold, Nicolai Maass, Ivo Meinhold-Heerlein, Wolfgang Wagner

Clinic of Gynecology and Obstetrics

37 Citations (Scopus)

Abstract

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 >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 >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.

Original language	English
Journal	Oncology
Volume	80
Issue number	1-2
Pages (from-to)	12-20
Number of pages	9
ISSN	0030-2414
DOIs	https://doi.org/10.1159/000327746
Publication status	Published - 06.2011

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title = "Progression-free survival in ovarian cancer is reflected in epigenetic DNA methylation profiles",

abstract = "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 >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 >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.",

author = "Dirk Bauerschlag and Ole Ammerpohl and Karen Br{\"a}utigam and Christian Schem and Qiong Lin and Weigel, {Marion T.} and Felix Hilpert and Norbert Arnold and Nicolai Maass and Ivo Meinhold-Heerlein and Wolfgang Wagner",

year = "2011",

month = jun,

doi = "10.1159/000327746",

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journal = "Oncology",

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T1 - Progression-free survival in ovarian cancer is reflected in epigenetic DNA methylation profiles

AU - Bauerschlag, Dirk

AU - Ammerpohl, Ole

AU - Bräutigam, Karen

AU - Schem, Christian

AU - Lin, Qiong

AU - Weigel, Marion T.

AU - Hilpert, Felix

AU - Arnold, Norbert

AU - Maass, Nicolai

AU - Meinhold-Heerlein, Ivo

AU - Wagner, Wolfgang

PY - 2011/6

Y1 - 2011/6

N2 - 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 >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 >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.

AB - 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 >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 >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.

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Progression-free survival in ovarian cancer is reflected in epigenetic DNA methylation profiles

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