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

Onkologie. 2007 Feb;30(1-2):14-9. doi: 10.1159/000096892. Epub 2007 Jan 26.

Abstract

Background: We investigated the hypermethylation status in serum of sporadic breast cancer patients.

Material and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins
  • Adult
  • Aged
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / blood*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / blood
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • DNA Methylation*
  • DNA Mutational Analysis / methods
  • Exonucleases / blood
  • Exonucleases / genetics
  • Exoribonucleases
  • Female
  • Genes, Tumor Suppressor*
  • Humans
  • Middle Aged
  • Neoplasm Proteins / blood
  • Neoplasm Proteins / genetics
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Ubiquitin-Protein Ligases / blood
  • Ubiquitin-Protein Ligases / genetics

Substances

  • 14-3-3 Proteins
  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16
  • Neoplasm Proteins
  • BRAP protein, human
  • Ubiquitin-Protein Ligases
  • Exonucleases
  • Exoribonucleases
  • SFN protein, human