Comparison of Methylation Profiling in Cancerous and Their Corresponding Normal Tissues from Korean Patients with Breast Cancer.
10.3343/alm.2013.33.6.431
- Author:
Eun Jung JUNG
1
;
In Suk KIM
;
Eun Yup LEE
;
Jeong Eun KANG
;
Sun Min LEE
;
Dong Chul KIM
;
Ju Yeon KIM
;
Soon Tae PARK
Author Information
1. Division of Surgical Oncology, Department of Surgery, Gyeongsang National University Hospital, Jinju, Korea.
- Publication Type:Original Article ; Comparative Study ; Research Support, Non-U.S. Gov't
- Keywords:
Breast cancer;
Epigenetics;
Carcinogenesis;
Methylation
- MeSH:
Adult;
Breast/metabolism;
Breast Neoplasms/*genetics/metabolism/pathology;
Cyclin-Dependent Kinase Inhibitor p15/genetics;
*DNA Methylation;
Female;
Humans;
Lymphatic Metastasis;
Middle Aged;
Promoter Regions, Genetic;
Republic of Korea;
Tumor Suppressor Proteins/genetics
- From:Annals of Laboratory Medicine
2013;33(6):431-440
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: Aberrant DNA hypermethylation plays a pivotal role in carcinogenesis and disease progression; therefore, accurate measurement of differential gene methylation patterns among many genes is likely to reveal biomarkers for improved risk assessment. We evaluated the gene hypermethylation profiles of primary breast tumors and their corresponding normal tissues and investigated the association between major clinicopathological features and gene hypermethylation. METHODS: A single reaction using methylation-specific multiplex ligation-dependent probe amplification was used to analyze the DNA methylation status of 24 tumor suppressor genes in 60 cancerous tissues and their corresponding normal tissues from patients with primary breast cancer. RESULTS: In cancerous breast tissues, 21 of 24 genes displayed promoter methylation in one or more samples. The most frequently methylated genes included RASSF1 (43.3%), APC (31.7%), CDKN2B (25.0%), CDH13 (23.3%), GSTP1 (16.7%), and BRCA1 (10%). APC was associated with lymph node metastasis, and BRCA1 was associated with negative estrogen receptor and negative progesterone receptor expression. In normal breast tissues, 8 of 24 tumor suppressor genes displayed promoter hypermethylation; CDKN2B (28.3%) and RASSF1 (8.3%) hypermethylation were most frequently observed. CONCLUSIONS: RASSF1 and CDKN2B hypermethylation in Korean breast cancer patients were the most frequent in cancerous tissue and corresponding normal tissue, respectively. Our data indicates that methylation of specific genes is a frequent event in morphologically normal breast tissues adjacent to breast tumors as well as the corresponding breast cancers. This study also suggests that gene methylation is linked to various pathological features of breast cancer; however, this requires confirmation in a larger study.
