title: Hypermethylation of tumor suppressor genes involved in critical regulatory pathways for developing a blood-based test in breast cancer.
abstract: BACKGROUND
  Aberrant DNA methylation patterns might be used as a biomarker for diagnosis and management of cancer patients.
  
  
  RESULTS
  To achieve a gene panel for developing a breast cancer blood-based test we quantitatively assessed the DNA methylation proportion of 248 CpG sites per sample (total of 31,248 sites in all analyzed samples) on 10 candidate genes (APC, BIN1, BMP6, BRCA1, CST6, ESR-b, GSTP1, P16, P21 and TIMP3). The number of 126 samples consisting of two different cohorts was used (first cohort: plasma samples from breast cancer patients and normal controls; second cohort: triple matched samples including cancerous tissue, matched normal tissue and serum samples). In the first cohort, circulating cell free methylated DNA of the 8 tumor suppressor genes (TSGs) was significantly higher in patients with breast cancer compared to normal controls (P<0.01). In the second cohort containing triple matched samples, seven genes showed concordant hypermethylated profile in tumor tissue and serum samples compared to normal tissue (P<0.05). Using eight genes as a panel to develop a blood-based test for breast cancer, a sensitivity and specificity of more than 90% could be achieved in distinguishing between tumor and normal samples.
  
  
  CONCLUSIONS
  Our study suggests that the selected TSG panel combined with the high-throughput technology might be a useful tool to develop epigenetic based predictive and prognostic biomarker for breast cancer relying on pathologic methylation changes in tumor tissue, as well as in circulation.
authors.affiliation: Laboratory for Gynecological Oncology, Department of Biomedicine, Women's Hospital, University of Basel, Basel, Switzerland.
authors.forename: Ramin
authors.initials: R
authors.lastname: Radpour
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Barekati
authors.forename: Corina
authors.initials: C
authors.lastname: Kohler
authors.forename: Qing
authors.initials: Q
authors.lastname: Lv
authors.forename: Nicole
authors.initials: N
authors.lastname: Bürki
authors.forename: Claude
authors.initials: C
authors.lastname: Diesch
authors.forename: Johannes
authors.initials: J
authors.lastname: Bitzer
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.forename: Seraina
authors.initials: S
authors.lastname: Schmid
authors.forename: Xiao Yan
authors.initials: XY
authors.lastname: Zhong
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood; D005260:Female; D053263:Gene Regulatory Networks; D052138:Genes, Neoplasm; D016147:Genes, Tumor Suppressor; D006801:Humans; D012680:Sensitivity and Specificity
chemical_list: D004273:DNA, Neoplasm