Abstract

We investigated the hypermethylation statusin serum of sporadic breast cancer patients. Materialand Methods: The hypermethylation status of BRCA1,p16 and 14-3-3s in cancerous tissues and the pairedserum of 38 sporadic breast cancer patients was examinedby methylation-specific PCR (MSP) assay. Normaland benign tissue and serum control DNA were also examinedto determine the specificity of hypermethylation.Results: Hypermethylation of 1 or more genes was foundin 36/38 (95%) of sporadic breast cancers. BRCA1 was hypermethylatedin 14/38 (37%), p16 in 13/38 (34%), and 14-3-3s in 33/38 (87%) of cancerous tissues. 71% of the correspondingserum DNA was positive for hypermethylation,including all histological types, stages and grades.No methylated products of BRCA1, p16 and 14-3-3s wereobserved in serum DNA from healthy women and patientswith benign tissue specimens. A gene unmethylatedin the tumor DNA was always found to be unmethylatedin matched serum DNA. Conclusions: Hypermethylationof BRCA1, p16 and 14-3-3s is present in all histologictypes, stages and grades in sporadic breast cancerand can be detected in serum DNA. It signifies thatserum-based hypermethylation screening may enhanceearly detection of sporadic breast cancer.

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