Hypermethylation of tumor suppressor genes BRCA1, p16 and 14-3-3sigma in serum of sporadic breast cancer patients.
BACKGROUND
We investigated the hypermethylation status in serum of sporadic breast cancer patients.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Jing
Feng
F
Department of Laboratory Medicine, Taihe Hospital, Yunyang Medical College, Shiyan, China.
Zhang
Jicai
J
Tao
Jianshu
J
Zhou
Youli
Y
Jun
Lu
L
Tang
Xuanbing
X
Wang
Yuping
Y
Hai
Huang
H
D048948:14-3-3 Proteins; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics*; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000097:blood / Q000235:genetics; D019175:DNA Methylation; D004252:DNA Mutational Analysis / Q000379:methods; D005092:Exonucleases / Q000097:blood / Q000235:genetics; D005095:Exoribonucleases; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood / Q000235:genetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D044767:Ubiquitin-Protein Ligases / Q000097:blood / Q000235:genetics
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; C111164:BRAP protein, human; D044767:Ubiquitin-Protein Ligases; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human