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KMID : 1134120070100010051
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Journal of Breast Cancer
2007 Volume.10 No. 1 p.51 ~ p.58
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Methylation Patterns of Cancer-Associated Genes in Breast Cancer
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Jee Sung-Bae
Park Woo-Chan
Kim Kee-Hwan
Kim Ji-Il
An Chang-Hyeok
Lim Keun-Woo
Oh Se-Jeong
Song Byung-Joo
Jung Sang-Seol
Kim Jeong-Soo
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Abstract
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Purpose: To investigate the methylation status of cancerassociated 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, RASSF1 , Twist, RAR , 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, RASSF1 , Twist, RAR \" and Cyclin D, were more frequently methylated in malignant than benign tumors, with the differences in the p14, p16, and RAR \" 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 RASSF1 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 RASSF1 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 RASSF1 , 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.
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KEYWORD
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Breast cancer, Tumor suppressor gene, Methylation
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