title: Basal-like breast cancer displays distinct patterns of promoter methylation.
abstract: Recent microarray profiling studies on breast cancer have identified distinct subtypes that are associated with different clinical outcomes. Promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of breast cancer. We proposed that immunohistopathologic subtypes of breast cancer are likely to contain distinct promoter methylation patterns. A panel of 10 gene promoters was assessed by quantitative multiplex methylation-specific PCR in 114 invasive ductal carcinomas from Korea representing the three major subtypes [57 luminal, 24 human epidermal growth factor 2 (HER2), and 33 basal-like] based on immunohistochemical findings of estrogen receptor, progesterone receptor, HER2, cytokeratin 5/6 and epidermal growth factor receptor. The median methylation levels of HIN1, RASSF1A and TWIST, and the average methylation ratio were significantly lower in basal-like subtype compared to luminal or HER2 subtypes. In contrast, BRCA1 methylation level was significantly higher in basal-like subtype than in luminal subtype. The methylation status of a panel of four genes (APC1, CDH, BRCA1 and RAR-β) in luminal and HER2 subtypes were dissimilar, where HER2 tumors showed a significantly higher level of methylation compared to luminal tumors. These results suggest that gene methylation in breast cancer can potentially serve as epigenetic biomarkers and may contribute further to current breast cancer classification.
authors.affiliation: Department of Pathology, Chonnam National University Medical School and Research Institute of Medical Sciences, Gwangju, South Korea.
authors.forename: Ji Shin
authors.initials: JS
authors.lastname: Lee
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Fackler
authors.forename: Jae Hyuk
authors.initials: JH
authors.lastname: Lee
authors.forename: Chan
authors.initials: C
authors.lastname: Choi
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Park
authors.forename: Jung Han
authors.initials: JH
authors.lastname: Yoon
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.forename: Saraswati
authors.initials: S
authors.lastname: Sukumar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000145:classification / Q000235:genetics*; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D020868:Gene Silencing; D019398:Genes, BRCA1; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic
chemical_list: D005819:Genetic Markers