J Breast Cancer.  2007 Mar;10(1):51-58. 10.4048/jbc.2007.10.1.51.

Methylation Patterns of Cancer-Associated Genes in Breast Cancer

Affiliations
  • 1Department of Surgery, The Catholic University of Korea, College of Medicine, Seoul, Korea. drbreast@catholic.ac.kr

Abstract

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. RESULT: 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 beta and Cyclin D, were more frequently methylated in malignant than benign tumors, with the differences in the p14, p16, and RAR beta 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 ubgroup 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.

Keyword

Breast cancer; Tumor suppressor gene; Methylation

MeSH Terms

Breast Neoplasms*
Breast*
Cadherins
Cyclin D
Diagnosis
DNA
Estrogens
Female
Genes, Tumor Suppressor
Humans
Methylation*
Polymerase Chain Reaction
Receptors, Progesterone
Cadherins
Cyclin D
DNA
Estrogens
Receptors, Progesterone

Figure

  • 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.


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