HOXA11 DNA methylation—A novel prognostic biomarker in ovarian cancer
Heidi Fiegl
Department of Gynecological Oncology, UCL EGA Institute for Women's Health, University College London, United Kingdom
Tyrolean Cancer Research Institute, Innsbruck, Austria
Search for more papers by this authorGudrun Windbichler
Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, Austria
Search for more papers by this authorElisabeth Mueller-Holzner
Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, Austria
Search for more papers by this authorGeorg Goebel
Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Innsbruck, Austria
Search for more papers by this authorMatthias Lechner
Department of Medicine, Christian Doppler Research Laboratory for Gut Inflammation, Innsbruck Medical University, Innsbruck, Austria
Search for more papers by this authorIan J. Jacobs
Department of Gynecological Oncology, UCL EGA Institute for Women's Health, University College London, United Kingdom
Search for more papers by this authorCorresponding Author
Martin Widschwendter
Department of Gynecological Oncology, UCL EGA Institute for Women's Health, University College London, United Kingdom
Fax: +44-20-7380-9748.
Department of Gynecological Oncology, UCL EGA Institute for Women's Health, University College London, EGA Hospital, 2nd Floor Huntley Street, London WC1E 6DH, UKSearch for more papers by this authorHeidi Fiegl
Department of Gynecological Oncology, UCL EGA Institute for Women's Health, University College London, United Kingdom
Tyrolean Cancer Research Institute, Innsbruck, Austria
Search for more papers by this authorGudrun Windbichler
Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, Austria
Search for more papers by this authorElisabeth Mueller-Holzner
Department of Obstetrics and Gynecology, Innsbruck Medical University, Innsbruck, Austria
Search for more papers by this authorGeorg Goebel
Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Innsbruck, Austria
Search for more papers by this authorMatthias Lechner
Department of Medicine, Christian Doppler Research Laboratory for Gut Inflammation, Innsbruck Medical University, Innsbruck, Austria
Search for more papers by this authorIan J. Jacobs
Department of Gynecological Oncology, UCL EGA Institute for Women's Health, University College London, United Kingdom
Search for more papers by this authorCorresponding Author
Martin Widschwendter
Department of Gynecological Oncology, UCL EGA Institute for Women's Health, University College London, United Kingdom
Fax: +44-20-7380-9748.
Department of Gynecological Oncology, UCL EGA Institute for Women's Health, University College London, EGA Hospital, 2nd Floor Huntley Street, London WC1E 6DH, UKSearch for more papers by this authorAbstract
Epigenetic alterations play a major role in cancer. Recently we reported that stem cell Polycomb group targets (PcGTs) are up to 12-fold more likely to have cancer-specific promoter DNA hypermethylation than nontargets. To identify potential, prognostic DNA methylation markers in ovarian cancer we analyzed the DNA methylation at 71 different loci in 22 ovarian cancers and 18 non-neoplastic ovarian specimens by means of a quantitative, real-time PCR-based technique (MethyLight). We identified DNA methylation of HOXA10 and HOXA11, both of them PcGTs, to be the best discriminators between cancer and non-neoplastic tissue. In an independent set consisting of 92 ovarian cancer specimens further analysis demonstrated that HOXA11 DNA methylation is (i) strongly associated with the residual tumor after cytoreductive surgery and (ii) is a marker indicating poor prognosis. HOXA11 DNA methylation was independently associated with poor outcome [relative risk for death 3.4 (95% CI 1.2–9.9; p = 0.03)]. These findings support the view that the technical inability to optimally cytoreduce ovarian cancer is associated with particular molecular alterations in the tumor which per se define a subgroup of patients with poor outcome. © 2008 Wiley-Liss, Inc.
Supporting Information
This article contains supplementary material available via the Internet at http://www.interscience.wiley.com/jpages/0020-7136/suppmat
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| ijc23563-Supplementary_Table_II.xls20.5 KB | Supporting Information file ijc23563-Supplementary_Table_II.xls |
| ijc23563-Supplementary_Table_III.xls25.5 KB | Supporting Information file ijc23563-Supplementary_Table_III.xls |
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