Abstract P2-06-06: ALU and LINE-1 hypomethylation is associated with HER2+/ER- subtype of breast cancer

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Abstract The changes in DNA methylation status in cancer cells are characterized by hypermethylation of promoter CpG islands and diffuse hypomethylation of non-coding genomic regions. ALU and long interspersed nucleotide element-1 (LINE-1) are non-coding genomic repetitive sequences and methylation of these elements can be used as a surrogate marker for genomewide methylation status. This study was designed to evaluate the changes of ALU and LINE-1 hypomethylation during breast cancer progression from normal to pre-invasive lesions and invasive breast cancer (IBC), and their relations with characteristics of IBC. We analyzed the methylation status of ALU and LINE-1 in 145 cases of breast samples including normal breast tissue (n = 30), atypical ductal hyperplasia/ flat epithelial atypia (ADH/FEA, n = 30), ductal carcinoma in situ (DCIS, n = 35) and IBC (n = 50), and another set of 129 cases of IBC by pyrosequencing. LINE-1 methylation was significantly decreased from normal to ADH/FEA, while ADH/FEA, DCIS and IBC were not different each other. There was no difference in ALU methylation levels during progression of breast cancer. In IBC, ALU hypomethylation was correlated with negative estrogen receptor (ER) status (p = 0.007) and LINE-1 hypomethylation was associated with negative ER status (p<0.001), positive HER2 status (p = 0.005) and p53 overexpression (p = 0.024). ALU-1 and LINE-1 methylation status was significantly different between breast cancer subtype and the HER2+/ER- subtype had significantly lower methylation levels and frequencies than the other subtypes. Our findings suggest that LINE-1 hypomethylation is an early event during breast cancer progression and prominent hypomethylation of ALU and LINE-1 in HER2+/ER- subtype may be related to chromosomal instability of this specific subtype. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-06-06.