P1-05-04: Distinct Patterns of Promoter CpG Island Methylation of Breast Cancer Subtype Are Associated with Different Stem Cell Phenotype.

Abstract

Abstract Background: Although DNA methylation profiles in breast cancer have been connected to breast cancer molecular subtype, there have been no studies of the association of DNA methylation with stem cell phenotype. This study was designed to evaluate promoter CpG islands methylation of 15 genes with regard to breast cancer subtype and to investigate whether the patterns of CpG island methylation in each subtype are associated with cancer stem cell phenotype represented by CD44+/CD24- or ALDH1 expression. Methods: We performed MethyLight analysis for the methylation status of 15 promoter CpG island loci involved in breast cancer progression (APC, DLEC1, GRIN2B, GSTP1, HOXA1, HOXA10, IGF2, MT1G, RARB, RASSF1A, RUNX3, SCGB3A1, SFRP1, SFRP4, and TMEFF2) and determined cancer stem cell phenotype by CD44/CD24 and ALDH1 immunohistochmeistry in 36 luminal A, 33 luminal B, 30 luminal-HER2, 40 HER2 enriched, and 40 basal-like subtypes of breast cancer. Results: The number of CpG island loci methylated was significantly different among subtypes and it was highest in luminal-HER2 subtype and lowest in basal-like subtype. Methylation frequencies and levels in 12 out of the 15 genes were significantly different among all subtypes and basal-like subtype showed significantly lower methylation frequencies and levels in nine genes, compared to luminal A, luminal B, HER2 enriched, and luminal-HER2 subtypes. CD44+/CD24- or ALDH1+ putative stem cell populations were most enriched in basal-like subtype. The methylation of promoter CpG islands was significantly lower in CD44+/CD24-cell (+) tumors, compared to CD44+/CD24-cell (−) tumors, even within the basal-like subtype. ALDH1 (+) tumors also had significantly lower methylation, compared to ALDH1 (−) tumors. Conclusions: Our findings showed that promoter CpG island methylation was significantly different according to breast cancer subtype and stem cell phenotype of tumor, suggesting that breast cancers have different methylation patterns according to molecular subtypes and it is associated with stem cell phenotypes of the tumor. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-05-04.