Basal-Like Breast Cancer Displays Distinct Promoter Methylation Profiles
SS Kim, CW Han, JS Lee, JH Lee, JH Nam, C Choi, MJ Fackler, S Sukumar. Chonnam National University Medical School, Gwangju, Republic of Korea; Johns Hopkins University School of Medicine, Baltimore, MD
Background: Recent microarray profiling studies on breast cancer have identified distinct subtypes that are associated with different clinical outcomes. Promoter methylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of breast cancer. We propose that distinct subtypes of breast cancer are likely to contain distinct promoter methylation profiles.
Design: A panel of 10 gene promoters was assessed by quantitative multiplex methylation-specific PCR in 114 invasive ductal carcinomas representing the three major subtypes (57 luminal, 24 HER2, and 33 basal-like) based on immunohistochemical findings of estrogen receptor, progesterone receptor, HER2, CK5/6, and epidermal growth factor receptor.
Results: Significant differences in methylation levels among the three subtypes of breast cancer were found for APC (p < 0.05), BRCA1 (p < 0.01), CDH1 (p < 0.05), HIN1 (p < 0.01), RASSF1A (p < 0.01), TWIST (p < 0.01), and cumulative methylation index (CMI) (p < 0.05). APC, HIN1, RASSF1A, and TWIST methylation levels and CMI were significantly lower in basal-like subtype compared to luminal or HER2 subtype, whereas BRCA1 methylation levels were significantly higher in basal-like subtype compared to luminal and HER2 subtypes. CDH1 methylation levels were significantly higher in HER2 subtype compared to luminal subtype.
Conclusions: Basal-like breast cancer displays differential methylation profiles compared to luminal and HER2 subtypes. Detection of methylation levels for some genes is potentially useful as epigenetic markers in breast cancer classification.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 31, Tuesday Afternoon