Hypermethylation of tumor suppressor genes BRCA1, p16 and 14-3-3sigma in serum of sporadic breast cancer patients.

We investigated the hypermethylation status in serum of sporadic breast cancer patients.,The hypermethylation status of BRCA1, p16 and 14-3-3sigma in cancerous tissues and the paired serum of 38 sporadic breast cancer patients was examined by methylation-specific PCR (MSP) assay. Normal and benign tissue and serum control DNA were also examined to determine the specificity of hypermethylation.,Hypermethylation of 1 or more genes was found in 36/38 (95%) of sporadic breast cancers. BRCA1 was hypermethylated in 14/38 (37%), p16 in 13/38 (34%), and 14- 3-3sigma in 33/38 (87%) of cancerous tissues. 71% of the corresponding serum DNA was positive for hypermethylation, including all histological types, stages and grades. No methylated products of BRCA1, p16 and 14-3-3sigma were observed in serum DNA from healthy women and patients with benign tissue specimens. A gene unmethylated in the tumor DNA was always found to be unmethylated in matched serum DNA.,Hypermethylation of BRCA1, p16 and 14-3-3sigma is present in all histologic types, stages and grades in sporadic breast cancer and can be detected in serum DNA. It signifies that serum-based hypermethylation screening may enhance early detection of sporadic breast cancer.