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Journal of Cancer Research and Clinical Oncology

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01.10.2007 | Original Paper

IGF-II promoter methylation and ovarian cancer prognosis

verfasst von: A. C. Beeghly, D. Katsaros, A. L. Wiley, I. A. Rigault de la Longrais, A. T. Prescott, H. Chen, M. Puopolo, T. J. Rutherford, H. Yu

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 10/2007

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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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Titel: IGF-II promoter methylation and ovarian cancer prognosis
verfasst von: A. C. Beeghly
D. Katsaros
A. L. Wiley
I. A. Rigault de la Longrais
A. T. Prescott
H. Chen
M. Puopolo
T. J. Rutherford
H. Yu
Publikationsdatum: 01.10.2007
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 10/2007
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-007-0211-3

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IGF-II promoter methylation and ovarian cancer prognosis

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Conclusions

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