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.
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.
Authors: Jana Jeschke; Leander Van Neste; Sabine C Glöckner; Mashaal Dhir; Marilia Freitas Calmon; Valérie Deregowski; Wim Van Criekinge; Ilse Vlassenbroeck; Alexander Koch; Timothy A Chan; Leslie Cope; Craig M Hooker; Kornel E Schuebel; Edward Gabrielson; Andreas Winterpacht; Stephen B Baylin; James G Herman; Nita Ahuja Journal: Epigenetics Date: 2012-07-01 Impact factor: 4.528
Authors: Marta Faryna; Carolin Konermann; Sebastian Aulmann; Justo Lorenzo Bermejo; Markus Brugger; Sven Diederichs; Joachim Rom; Dieter Weichenhan; Rainer Claus; Michael Rehli; Peter Schirmacher; Hans-Peter Sinn; Christoph Plass; Clarissa Gerhauser Journal: FASEB J Date: 2012-08-28 Impact factor: 5.191
Authors: Mary Jo Fackler; Christopher B Umbricht; Danielle Williams; Pedram Argani; Leigh-Ann Cruz; Vanessa F Merino; Wei Wen Teo; Zhe Zhang; Peng Huang; Kala Visvananthan; Jeffrey Marks; Stephen Ethier; Joe W Gray; Antonio C Wolff; Leslie M Cope; Saraswati Sukumar Journal: Cancer Res Date: 2011-08-08 Impact factor: 12.701
Authors: K P M Suijkerbuijk; M J Fackler; S Sukumar; C H van Gils; T van Laar; E van der Wall; M Vooijs; P J van Diest Journal: Ann Oncol Date: 2008-07-22 Impact factor: 32.976
Authors: Cathy B Moelans; Eva J Vlug; Cigdem Ercan; Peter Bult; Horst Buerger; Gabor Cserni; Paul J van Diest; Patrick W B Derksen Journal: Cell Oncol (Dordr) Date: 2015-09-21 Impact factor: 6.730