Promoter hypermethylation is an early event in breast carcinogenesis.

Abstract

Abstract Abstract #5041 Background. Aberrant methylation of CpG islands in the promoter region of tumor suppressor genes has become established as an important epigenetic mechanism for gene silencing. Promoter hypermethyaltion in precursor lesions at risk for progression to invasive cancer may be biomarkers of cancer risk and targets for cancer chemoprevention. In breast cancer promoter hypermethylation has been described for several genes covering all aspects of cellular function. However, the methylation studies of precursor lesion of the breast are rather sparse and mostly done in a purely qualitative manner.
 Design. To evaluate the significance of alterations in promoter hypermethylation during multistage carcinogenesis of the breast, quantitative multiplex methylation-specific PCR of six genes (APC1, Cyclin D2, HIN-1, RAR-b, RASSF1A, and Twist) was performed on DNA from 15 normal breast tissues, 21 usual ductal hyperplasia (UDH), 48 ductal carcinoma in situ (DCIS), and 35 stage I invasive ductal carcinoma (IDC), not otherwise specified.
 Results. We found no to very low levels of promoter methylation in normal samples. In general UDH, DCIS, and IDC samples revealed varying levels of methylation ranging from 0 to 100%. One-way analysis of variance showed that the methylation levels of all six genes increased significantly with the progression of breast neoplasia from normal epithelium, through hyperplasia, to DCIS. However, methylation levels were not significantly different between DCIS and IDC.
 Conclusion. Our results suggest that promoter hypermethylation is an early event in breast carcinogenesis. Promoter hypermethylation in the precursor lesions of the breast cancer may be used as a target for cancer chemoprevention. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5041.