Validation of DNA promoter hypermethylation biomarkers in breast cancer - A short report

Jolien S. De Groot, Xiaojuan Pan, Jan Meeldijk, Elsken Van Der Wall, Paul J. Van Diest, Cathy B. Moelans

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: DNA promoter hypermethylation of tumor suppressor genes is known to occur early in cancer development, including breast cancer. To improve early breast cancer detection, we aimed to investigate whether the identification of DNA promoter hypermethylation might be of added value. Methods: The methylation status of a panel of 19 candidate genes (AKR1B1, ALX1, ARHGEF7, FZD10, GHSR, GPX7, GREM1, GSTP1, HOXD1, KL, LHX2, MAL, MGMT, NDRG2, RASGRF2, SFRP1, SFRP2, TM6SF1 and TMEFF2) was determined in formalin-fixed paraffin-embedded normal breast and breast cancer tissue samples using gel-based methylation-specific PCR (MSP). Results: The promoters of the AKR1B1, ALX1, GHSR, GREM1, RASGRF2, SFRP2, TM6SF1 and TMEFF2 genes were found to be significantly differentially methylated in normal versus malignant breast tissues. Based on sensitivity, specificity and logistic regression analyses the best performing genes for detecting breast cancer were identified. Through multivariate analyses, we found that AKR1B1 and TM6SF1 could detect breast cancer with an area under the curve (AUC) of 0.986 in a receiver operating characteristic (ROC) assessment. Conclusions: Based on our data, we conclude that AKR1B1 and TM6SF1 may serve as candidate methylation biomarkers for early breast cancer detection. Further studies are underway to evaluate the methylation status of these genes in body fluids, including nipple aspirates and blood.

Original languageEnglish (US)
Pages (from-to)297-303
Number of pages7
JournalCellular Oncology
Volume37
Issue number4
DOIs
StatePublished - Aug 2014

Keywords

  • Biomarkers
  • Breast cancer
  • DNA promoter hypermethylation
  • Early detection
  • Validation

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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