J Breast Cancer.  2007 Jun;10(2):120-126. 10.4048/jbc.2007.10.2.120.

Adenomatous Polyposis Coli and Ras Association Domain Family 1A Gene Methylation in Breast Cancer Patients

• Park IK
• Yim JS
• Ra YM
• Ko DG
• Choi IS
• Choi WJ
• Yoon DS

• KMID: 1745052
• DOI: http://doi.org/10.4048/jbc.2007.10.2.120

Abstract

PURPOSE: Of the many carcinogenic mechanisms, DNA methylation is a strong factor in various cancers, including cancer of the breast. The genes related to breast cancer include 14.3.3 sigma, Cyclin D2, RARbeta, Twist, Ras association domain family 1A gene (BASSF1A), HIN-1, p16, and Adenomatous polyposis coli (APC). Of these, hypermethylation of the APC and RASSF1A genes is, found in breast cancer patients, and especially in those with a poor prognosis. This study investigated whether hypermethylation of the APC and RASSF1A genes is related with breast cancer metastasis.
METHODS
Of the 110 patients who received surgical operation at our hospital's department of surgery from January 2001 to December 2003, 16 patients with metastatic lesion found during the follow-up period were selected. Seventeen patients without metastasis selected as the tissue group after considering their age, cancer stage, and physical state. Forty seven patients were selected as the serum group, including 6 patients with metastasis, and they were evaluated for metastasis and methylation. Serum and tissue were collected and after being processed by the methylation specific PCR (MSP), and the methylation of the APC and RASSF1A genes was observed.
RESULTS
In the tissue study group, the APC gene methylation ratio of the patients whose stages are between the stage 2 and 3 was 50:94%, and that of RASSF1A gene methylation was 68.7:65% respectively. Methylation rates of both genes was found in 42.9% of the stage 2 recurrent patients (non-recurrent patients: 22%) and in 77.8% (non-recurrent patients: 50%) in stage 3 recurrent patients. In the serum study group, a statistical correlation was shown (p=0.013) between methylation of RASSF1A and recurrence, where 5 of the 16 patients with methylation showed recurrences and only 1 patient of the 31 nonmethylated patients showed recurrence.
CONCLUSION
We determined the correlation between APC and RASSF1A methylation and recurrence of breast cancer. Further studies with large sample populations and more advanced method are needed to confirm our findings.

Keyword

Breast Cancer; DNA methylation; APC; RASSF1A

MeSH Terms

Adenomatous Polyposis Coli*
Breast Neoplasms*
Breast*
Cyclin D2
DNA Methylation
Follow-Up Studies
Genes, APC
Humans
Methylation*
Neoplasm Metastasis
Polymerase Chain Reaction
Prognosis
Recurrence
Cyclin D2

Figure

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  Fig 1 MSP of APC and RASSF1A genes in breast tissues of stage II group.

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  Fig 2 MSP of APC and RASSF1A genes in breast tissues of stage III group.

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  Fig 3 MSP of APC and RASSF1A genes in blood of 47 patients. Stge 0, I: 5, 6, 8, 10, 11, 12, 16, 20, 21, 25, 29, 34, 46, 47, 51. Stage II: 1, 2, 4, 13, 15, 18, 23, 26, 28, 30, 32, 33, 35, 36, 37, 40, 41, 42, 43, 48, 50, 52, 54. Stage III: 3, 7, 14, 17, 27, 31, 38, 45, 53. *: recurred cases.

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