Integrative genome-wide expression and promoter DNA methylation profiling identifies a potential novel panel of ovarian cancer epigenetic biomarkers

Gloss, Brian S.; Patterson, Kate I.; Barton, Caroline A.; Gonzalez, Maria; Scurry, James P.; Hacker, Neville F.; Sutherland, Robert L.; O’Brien, Philippa M.; Clark, Susan J.

doi:10.1016/j.canlet.2011.12.003

« Previous Next »Cancer Letters
Volume 318, Issue 1 , Pages 76-85, 1 May 2012

Integrative genome-wide expression and promoter DNA methylation profiling identifies a potential novel panel of ovarian cancer epigenetic biomarkers

Brian S. Gloss
- Cancer Research Program, The Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia
Kate I. Patterson
- Cancer Research Program, The Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia
Caroline A. Barton
- Cancer Research Program, The Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia
Maria Gonzalez
- Cancer Research Program, The Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia
James P. Scurry
- Hunter Area Pathology Service, John Hunter Hospital, New Lambton, New South Wales 2310, Australia
Neville F. Hacker
- Gynaecological Cancer Centre, Royal Hospital for Women, Randwick, New South Wales 2031, Australia
Robert L. Sutherland
- Cancer Research Program, The Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia
- St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, New South Wales 2052, Australia
Philippa M. O’Brien
- Cancer Research Program, The Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia
- St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, New South Wales 2052, Australia
- Equal last authors.
Susan J. Clark
- Cancer Research Program, The Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia
- St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, New South Wales 2052, Australia
- Corresponding author. Address: Epigenetic Research Laboratory, Cancer Research Program, The Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia. Tel.: +61 2 92958315; fax: +61 2 92958316.
- Equal last authors.

Received 16 August 2011; received in revised form 11 November 2011; accepted 2 December 2011. published online 29 December 2011.

Abstract

To identify epigenetic-based biomarkers for diagnosis of ovarian cancer we performed MeDIP-Chip in A2780 and CaOV3 ovarian cancer cell lines. Validation by Sequenom massARRAY methylation analysis confirmed a panel of six gene promoters (ARMCX1, ICAM4, LOC134466, PEG3, PYCARD & SGNE1) where hypermethylation discriminated 27 serous ovarian cancer clinical samples versus 12 normal ovarian surface epithelial cells (OSE) (ROC of 0.98). Notably, CpG sites across the transcription start site of a potential long-intergenic non-coding RNA (lincRNA) gene (LOC134466), was shown to be hypermethylated in 81% of serous EOC and could differentiate tumours from OSE (p<0.05). We propose that this potential biomarker panel holds great promise as a diagnostic test for high-grade (Type II) serous ovarian cancer.