IGF-II promoter methylation and ovarian cancer prognosis.

Beeghly AC, Katsaros D, Wiley AL, Rigault de la Longrais IA, Prescott AT, Chen H, Puopolo M, Rutherford TJ, Yu H
J Cancer Res Clin Oncol. 2007 133 (10): 713-23

PMID: 17569086 · DOI:10.1007/s00432-007-0211-3

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.

MeSH Terms (16)

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

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