Abstract #LB-165: Association between frequent CpG island methylation and HER2 amplification in human breast cancers

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO The presence of frequent methylation of CpG islands, designated as the CpG island methylator phenotype in some cancers, is associated with distinct clinicopathological characteristics, including gene amplification, in individual tumor types. Amplification of HER2 in human breast cancers is an important prognostic and therapeutic target, but an association between HER2 amplification and frequent CpG island methylation is unknown. To clarify the association, we here quantified methylation levels of promoter CpG islands of 11 genes, which are unlikely to confer growth advantage to cells, in 63 human breast cancers. The number of methylated genes in a cancer did not obey a bimodal distribution, and the 63 cancers were classified into those with frequent methylation (n=16), moderate methylation (n=26), and no methylation (n=21). The incidence of HER2 amplification was significantly higher in the cancers with frequent methylation (11 of 16) than in those with no methylation (2 of 21, P=0.001). Also, the number of methylated genes correlated with the degree of HER2 amplification (r=0.411, P=0.002). Correlation analysis with clinicopathological characteristics and methylation of CDKN2A, BRCA1, and CDH1 revealed that frequent methylation had significant correlation with higher nuclear grades (P=0.001). These showed that frequent methylation had a strong association with HER2 amplification in breast cancers, and suggested that frequent methylation can be a determinant of various characteristics in a fraction of human breast cancers. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-165.