title: Comparison of methylation profiling in cancerous and their corresponding normal tissues from korean patients with breast cancer.
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.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Jung
authors.forename: In-Suk
authors.initials: IS
authors.lastname: Kim
authors.forename: Eun Yup
authors.initials: EY
authors.lastname: Lee
authors.forename: Jeong-Eun
authors.initials: JE
authors.lastname: Kang
authors.forename: Sun-Min
authors.initials: SM
authors.lastname: Lee
authors.forename: Dong Chul
authors.initials: DC
authors.lastname: Kim
authors.forename: Ju-Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Park
mesh_terms: D000328:Adult; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D056910:Republic of Korea; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins
keywords: Breast cancer; Carcinogenesis; Epigenetics; Methylation