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.
  
  
  CONCLUSIONS
  Epigenetic modifications at specific CpG sites correlate with PFI in ovarian cancer. Therefore, such analysis might be of prognostic value.
authors.affiliation: Department of Gynecology, University Medical Center Aachen, RWTH, Aachen, Germany. dbauerschlag@ukaachen.de
authors.forename: Dirk O
authors.initials: DO
authors.lastname: Bauerschlag
authors.forename: Ole
authors.initials: O
authors.lastname: Ammerpohl
authors.forename: Karen
authors.initials: K
authors.lastname: Bräutigam
authors.forename: Christian
authors.initials: C
authors.lastname: Schem
authors.forename: Qiong
authors.initials: Q
authors.lastname: Lin
authors.forename: Marion T
authors.initials: MT
authors.lastname: Weigel
authors.forename: Felix
authors.initials: F
authors.lastname: Hilpert
authors.forename: Norbert
authors.initials: N
authors.lastname: Arnold
authors.forename: Nicolai
authors.initials: N
authors.lastname: Maass
authors.forename: Ivo
authors.initials: I
authors.lastname: Meinhold-Heerlein
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wagner
mesh_terms: D017024:Chemotherapy, Adjuvant; D003596:Cytosine / Q000737:chemistry; D019175:DNA Methylation / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D046228:Microarray Analysis; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D017422:Sequence Analysis, DNA; D013997:Time Factors
chemical_list: D003596:Cytosine