IGF-II promoter methylation and ovarian cancer prognosis.

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.

• Authors: 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
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 133 Issue 10 Pg. 713-23 (Oct 2007) ISSN: 0171-5216 [Print] Germany
• PMID: 17569086 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin-Like Growth Factor II

Topics

• Adult
• Aged
• Aged, 80 and over
• DNA Methylation
• Female
• Humans
• Insulin-Like Growth Factor II (genetics)
• Kaplan-Meier Estimate
• Middle Aged
• Neoplasm Staging
• Neoplasms, Glandular and Epithelial (genetics, mortality, pathology)
• Ovarian Neoplasms (genetics, mortality, pathology)
• Polymerase Chain Reaction
• Prognosis
• Promoter Regions, Genetic (genetics)
• Survival Analysis