Published online Mar 31, 2007.
https://doi.org/10.4048/jbc.2007.10.1.51
Methylation Patterns of Cancer-Associated Genes in Breast Cancer
Abstract
Purpose
To investigate the methylation status of cancer-associated genes in breast cancer to assess its use in the diagnosis of breast cancer and the relationship with distinctive clinical and pathological features.
Methods
A total of 29 benign tumors and their adjacent normal tissues as well as 67 malignant tumors and adjacent normal samples, from women undergoing surgery for primary invasive breast carcinoma at Uijongbu St. Mary's Hospital, between March 2003 and March 2005, were used. Eleven candidate genes were chosen; P14, P16, DAPK, MGMT, h-MLH, E-cadherin, RASSF1α, Twist, RARβ, HIN-1, and Cyclin D. DNA was extracted from fresh tissues, and methylation specific PCR performed.
Results
The number of methylated genes was increased in the malignant tissues compared to the benign tumors and adjacent normal tissues. 7 genes; P14, P16, MGMT, RASSF1α, Twist, RARβ, and Cyclin D, were more frequently methylated in malignant than benign tumors, with the differences in the p14, p16, and RARβ, genes were statistically significant (p<0.05). In benign tumors, the p16 and HIN-1 genes were the most infrequently (6.9%) and frequently methylated (82.8%), respectively. In malignant tumors, the h-MLH and RASSF1α genes were most infrequently and frequently methylated genes, respectively. The subgroup showing methylation of the DAPK gene had a higher nuclear grade and greater progesterone receptor negativity. The group in which the RASSF1α gene was methylated, had greater estrogen receptor (ER) and progesterone receptor (PgR) positivities. The Twist gene was frequently methylated in the subgroup showing higher nuclear and histologic grades. The group with HIN-1 and cyclin D methylation had a tendency to show greater ER positivity.
Conclusion
The subgroups showing methylated DAPK and Twist should be more intensely treated and followed up more carefully than those with RASSF1α, HIN-1 and Cyclin D methylation. Gene methylation may be linked to various pathological features of breast cancer; however, this will require confirmation from larger studies.
Fig 1
Number of methylated genes, benign tumor vs. normal tissue.
Fig 2
Number of methylated genes, malignant tumor vs. normal tissue.
Fig 3
The correlation of numbers of methylated genes between normal tissue vs. malignant tumor.
Fig 4
The correlation of numbers of methylated genes between normal tissue vs. benign tumor.
Table 1
Genes investigated in this study
Table 2
Characteristics of breast cancer patients
Table 3
MS-PCR primers of specific genes analyzed in this study
Table 4
Comparision of numbers of hypermethylation in 11 genes
Table 5
The comparison of methylation status of each gene, benign tumor vs. malignant tumor
Table 6
The comparison of methylation status of each gene, normal tissue vs. malignant tumor
Table 7
Logistic regression of hypermethylation status, benign tumor vs. malignant tumor
Table 8
Logistic regression of hypermethylation status, normal tissue vs. malignant tumor
Table 9
Association between gene promoter methylation and clinicopathological features
References
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