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. 2010 Jul;30(7):2489-96.

Aberrant promoter hypermethylation and genomic hypomethylation in tumor, adjacent normal tissues and blood from breast cancer patients

Yoon Hee Cho  1 , Hulya Yazici, Hui-Chen Wu, Mary Beth Terry, Karina Gonzalez, Mengxue Qu, Nejat Dalay, Regina M Santella
Affiliations

Aberrant promoter hypermethylation and genomic hypomethylation in tumor, adjacent normal tissues and blood from breast cancer patients

Yoon Hee Cho et al. Anticancer Res. 2010 Jul.

Abstract

Background: Promoter hypermethylation and global hypomethylation in the human genome are hallmarks of most cancers. Detection of aberrant methylation in white blood cells (WBC) has been suggested as a marker for cancer development, but has not been extensively investigated. This study was carried out to determine whether aberrant methylation in WBC DNA can be used as a surrogate biomarker for breast cancer risk.

Patients and methods: Promoter hypermethylation of 8 tumor suppressor genes (RASSF1A, APC, HIN1, BRCA1, CYCLIND2, RARbeta, CDH1 and TWIST1) and DNA methylation for three repetitive elements (LINE1, Sat2 and Alu) were analyzed in invasive ductal carcinoma of the breast, paired adjacent normal tissue and WBC from 40 breast cancer patients by the MethyLight assay. Methylation in WBC from 40 controls was also analyzed.

Results: Tumor and adjacent tissues showed frequent hypermethylation for all genes tested, while WBC DNA was rarely hypermethylated. For HIN1, RASSF1A, APC and TWIST1, there was agreement between hypermethylation in tumor and adjacent tissues (p=0.04, p=0.02, p=0.005 and p<0.0001, respectively). DNA methylation for the three repetitive elements was lower in tumor compared to adjacent tissue and WBC DNA. Significant correlations in the methylation of Sat2M1 between tumor and adjacent tissues and WBC DNA were found (p<0.0001 and p=0.046, respectively). There was also a significant difference in methylation of Sat2M1 between cases and controls (p=0.01).

Conclusion: These results suggest that further studies of WBC methylation, including prospective studies, may provide biomarkers of breast cancer risk.

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Figures

Figure 1
Figure 1
Map of gene promoter methylation in blood, normal adjacent- and tumor tissues. Box color represents the degree of methylation (light gray, 1≤ % methylation <4; dark gray, 4 ≥ % methylation <10; black, 10 ≥ % methylation).
Figure 2
Figure 2
Comparison of (A) LINE1, (B) Sat2M1 and (C) AluM2 hypomethylation levels from tumor (n =40), normal adjacent tissues (n =27) and WBC DNA (n =40 for both cases and controls). Hypomethylation levels in LINE1 and Sat2M1 in tumor tissue was significantly decreased compared with those in WBC DNA (*both P<0.0001, Wilcoxon test). Significant correlations in methylation of LINE1 between tumor and WBC DNA (†Rho =0.46; P =0.0031, Spearman’s rank correlation test) and methylation of Sat2M1 between tumor and adjacent normal tissues (†Rho=0.78; P<0.0001), tumor and WBC DNA (†Rho =0.32; P =0.046) or adjacent normal tissue and WBC DNA (†Rho=0.67; P=0.002) were shown. Methylation of Sat2M1 in WBC DNA was significantly different between cases and control (§P=0.01, Wilcoxon test). Data represent the means ± SD (error bars).
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References

    1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer Statistics, 2009. CA Cancer J Clin. 2009;59:225–249. - PubMed
    1. Rosenberg K. Ten-year risk of false positive screening mammograms and clinical breast examinations. J Nurse-Midwifery. 1998;43:394–395. - PubMed
    1. Müller HM, Widschwendter A, Fiegl H, Ivarsson L, Goebel G, Perkmann E, Marth C, Widschwendter M. DNA methylation in serum of breast cancer patients: an independent prognostic marker. Cancer Res. 2003;63:7641–7645. - PubMed
    1. Merlo A, Herman JG, Mao L, Lee DJ, Gabrielson E, Burger PC, Baylin SB, Sidransky D. 5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers. Nat Med. 1995;1:686–692. - PubMed
    1. Laird PW. The power and the promise of DNA methylation markers. Nat Rev Cancer. 2003;3:253–266. - PubMed

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