Diagnostic values of GHSR DNA methylation pattern in breast cancer

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• 作者：Sandeep Kumar Botla (1)
  Amin Moghaddas Gholami (2)
  Mahdi Malekpour (34)
  Evgeny A. Moskalev (1)
  Mahdi Fallah (5)
  Pouria Jandaghi (16)
  Ali Aghajani (7)
  Irina S. Bondar (8)
  Ramesh Omranipour (3)
  Fatemeh Malekpour (9)
  Abbas Mohajeri (10)
  Azin Jahangiri Babadi (1)
  ?zgür Sahin (11)
  Vladimir V. Bubnov (12)
  Hossein Najmabadi (7)
  J?rg D. Hoheisel (1)
  Yasser Riazalhosseini (113) y.riazalhosseini@dkfz.de
• 关键词：DNA methylation – Breast cancer – Diagnosis – GHSR – Epigenetics
• 刊名：Breast Cancer Research and Treatment
• 出版年：2012
• 出版时间：October 2012
• 年：2012
• 卷：135
• 期：3
• 页码：705-713
• 全文大小：458.3 KB
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• 作者单位：1. Division of Functional Genome Analysis, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany2. Chair of Proteomics and Bioanalytics, Technische Universit?t München, 85354 Freising, Germany3. Imam Khomeini Hospital, Cancer Institute, Tehran University of Medical Sciences, 1145765111 Tehran, Iran4. Department of Medicine, Vanderbilt University Medical Center, S-3223 MCN, Nashville, TN 37232-2372, USA5. Division of Molecular Genetic Epidemiology, German Cancer Research Center, (DKFZ), 69120 Heidelberg, Germany6. Research Center of Medical Sciences, I.A.U, Tehran Medical Branch, Tehran, Iran7. Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, 3834198571 Tehran, Iran8. Regional Oncology Clinic, Odessa, 265026 Ukraine9. Shohada Tajrish Hospital, Shahid Beheshti University of Medical Sciences, 19899-34148 Tehran, Iran10. Department of Research and Development, Zahravi Pharmaceutical Company, 51575-5367 Tabriz, Iran11. Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany12. Department of Genomics and Immunology, Odessa State Medical University, 265026 Odessa, Ukraine13. Department of Human Genetics, McGill University and Genome Quebec Innovation Centre, 740 Dr. Penfield Ave., Montreal, QC H3A 0G1, Canada
• ISSN：1573-7217

文摘

DNA methylation patterns have been recognised as cancer-specific markers with high potential for clinical applications. We aimed at identifying methylation variations that differentiate between breast cancers and other breast tissue entities to establish a signature for diagnosis. Candidate genomic loci were analysed in 117 fresh-frozen breast specimens, which included cancer, benign and normal breast tissues from patients as well as material from healthy individuals. A cancer-specific DNA methylation signature was identified by microarray analysis in a test set of samples (n = 52, p < 2.1 × 10?4) and its performance was assessed through bisulphite pyrosequencing in an independent validation set (n = 65, p < 1.9 × 10?7). The signature is associated with SFRP2 and GHSR genes, and exhibited significant hypermethylation in cancers. Normal-appearing breast tissues from cancer patients were also methylated at these loci but to a markedly lower extent. This occurrence of methylated DNA in normal breast tissue of cancer patients is indicative of an epigenetic field defect. Concerning diagnosis, receiver operating characteristic curves and the corresponding area under the curve (AUC) analysis demonstrated a very high sensitivity and specificity of 89.3 and 100 %, respectively, for the GHSR methylation pattern (AUC >0.99). To date, this represents the DNA methylation marker of the highest sensitivity and specificity for breast cancer diagnosis. Functionally, ectopic expression of GHSR in a cell line model reduced breast cancer cell invasion without affecting cell viability upon stimulation of cells with ghrelin. Our data suggest a link between epigenetic down-regulation of GHSR and breast cancer cell invasion.