In the present study, we determined the gene hypermethylation profiles of normal tissues adjacent to invasive breast carcinomas and investigated whether these are associated with the gene hypermethylation profiles of the corresponding primary breast tumours.

A quantitative methylation−specific PCR assay was used to analyse the DNA methylation status of 6 genes (DAPK, TWIST, HIN−1, RASSF1A, RARbeta2 and APC) in 9 normal breast tissue samples from unaffected women and in 56 paired cancerous and normal tissue samples from breast cancer patients.

Normal tissue adjacent to breast cancer displayed statistically significant differences to unrelated normal breast tissues regarding the aberrant methylation of the RASSF1A, RARbeta2 and APC genes. Although methylation ratios in normal tissues from cancer patients were significantly lower than in the cancerous tissue from the same patient, in general, a clear correlation was observed between methylation ratios measured in both tissue types for all genes tested. When analysed as a categorical variable, there was a significant concordance between methylation changes in normal tissues and in the corresponding tumour for all genes tested but RASSF1A. Notably, in 73% of patients, at least one gene with an identical methylation change in cancerous and normal breast tissues was observed.

Histologically normal breast tissues adjacent to breast tumours frequently exhibit methylation changes in multiple genes. These methylation changes may play a role in the earliest stages of the development of breast neoplasia.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.