This study was conducted to mine novel breast-specific unigenes and analyze their epigenetic regulation in breast cancer. Differential digital display and methylation analysis identified the Hs.137007 gene containing a Kelch domain as a candidate novel epigenetic marker. In 50 pairs of breast cancer tissues and nearby normal tissues the methylation level of the 14 CpG sites at the promoter region (−778 to −485) of the gene was higher in cancer tissues (72-93%) than in normal tissues (31-83%), with a high correlation rate (p<0.05). End-point RT-PCR and real-time RT-PCR revealed that Hs.137007 was up-regulated in cancer tissues. A clear relationship between high methylation levels and up-regulated expression was also observed in the cultured breast cell lines. The MCF7 (90-100%) and MDAMB468 (100%) cancer cell lines that showed higher methylation than the BT549 (20-90%) and 184B5 (10-100%) at the 14 CpGs also showed elevated gene expression. Taken together, these results indicate that the Hs.137007 gene is a novel gene specifically expressed in the breast that can be utilized as an epigenetic marker of breast cancer.

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