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IGF-II promoter methylation and ovarian cancer prognosis

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Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

The insulin-like growth factor-II (IGF-II) gene has four promoters that produce distinct transcripts which vary by tissue type and developmental stage. Dysregulation of normal promoter usage has been shown to occur in cancer; DNA methylation regulates promoter use. Thus, we sought to examine if DNA methylation varies among IGF-II promoters in ovarian cancer and if methylation patterns are related to clinical features of the disease.

Study design

Tumor tissue, clinical data, and follow-up information were collected from 215 patients diagnosed with primary epithelial ovarian cancer. DNA extracted from tumor tissues was analyzed for IGF-II promoter methylation with seven methylation specific PCR (MSP) assays: three for promoter 2 (P2) and two assays each for promoters 3 and 4 (P3 and P4).

Results

Methylation was found to vary among the seven assays: 19.3% in P2A, 45.6% in P2B, 50.9% in P2C, 48.4% in P3A, 13.1% in P3B, 5.1% in P4A, and 6.1% in P4B. Methylation in any of the three P2 assays was associated with high tumor grade (P = 0.043), suboptimal debulking (P = 0.036), and disease progression [hazards ratio (HR) = 1.73, 95% confidence interval (CI) 1.09–2.74]. When comparing promoter methylation patterns, differential methylation of P2 and P3 was found to be associated with disease prognosis; patients with P3 but not P2 methylation were less likely to have disease progression (HR = 0.39, 95% CI 0.17–0.91) compared to patients with P2 but not P3 methylation.

Conclusions

This study shows that methylation varies among three IGF-II promoters in ovarian cancer and that this variation seems to have biologic implications as it relates to clinical features and prognosis of the disease.

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Acknowledgments

This research was supported in part by the NIH grant R01AG21392, the Anna Fuller Fund from the Yale University School of Medicine, Department of Pathology (A. Beeghly), and the Associazione Italiana per la Ricerca sul Cancro (D. Katsaros).

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Authors and Affiliations

  1. Department of Epidemiology and Public Health, Yale University School of Medicine and Yale Cancer Center, 60 College Street, New Haven, CT, 06520-8034, USA

    A. C. Beeghly, A. L. Wiley, A. T. Prescott, H. Chen, T. J. Rutherford & H. Yu

  2. University of Turin, Turin, Italy

    D. Katsaros, I. A. Rigault de la Longrais & M. Puopolo

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  1. A. C. Beeghly
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  2. D. Katsaros
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  3. A. L. Wiley
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  4. I. A. Rigault de la Longrais
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  5. A. T. Prescott
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  6. H. Chen
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  7. M. Puopolo
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  8. T. J. Rutherford
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  9. H. Yu
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Correspondence to H. Yu.

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Beeghly, A.C., Katsaros, D., Wiley, A.L. et al. IGF-II promoter methylation and ovarian cancer prognosis. J Cancer Res Clin Oncol 133, 713–723 (2007). https://doi.org/10.1007/s00432-007-0211-3

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  • DOI: https://doi.org/10.1007/s00432-007-0211-3

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