OBJECTIVES: We have recently shown that detection of CST6 promoter methylation in primary breast tumors can provide important prognostic information in patients with operable breast cancer and that CST6 promoter is also methylated in Circulating Tumor Cells (CTC). In this study we evaluated the presence of CST6 promoter methylation in cell-free DNA (cfDNA) circulating in plasma of breast cancer patients. DESIGN AND METHODS: Our study material consisted of: a) a pilot testing group of 27 patients with stage I-III operable breast cancer, 46 patients with verified metastasis and 37 healthy donors and b) an independent cohort of 123 consecutive stage I-III operable breast cancer patients. Methylated and unmethylated CST6 promoter sequences were detected by using methylation-specific PCR (MSP). CST6 immunohistochemical detection was performed in 20 corresponding primary tumor tissues. RESULTS: In the pilot testing group, CST6 promoter was methylated in 8/27 (29.6%) operable breast cancer patients, in 6/46 (13.0%) patients with verified metastasis but none of 37 healthy individuals (0%). In the independent cohort, 49/123 (39.8%) operable breast cancer patients were found positive. During the follow up period, 25/123 (20.3%) patients relapsed and 9/123 (7.3%) died. CST6 was methylated in cfDNA of 13/25 (52%) patients that relapsed and in 3/9 (33.3%) patients that died. CONCLUSIONS: CST6 promoter is highly methylated in cfDNA of breast cancer patients, but not in healthy individuals. CST6 promoter methylation in cfDNA, should be prospectively validated as a novel plasma tumor biomarker for breast cancer in a large cohort of breast cancer patients.
OBJECTIVES: We have recently shown that detection of CST6 promoter methylation in primary breast tumors can provide important prognostic information in patients with operable breast cancer and that CST6 promoter is also methylated in Circulating Tumor Cells (CTC). In this study we evaluated the presence of CST6 promoter methylation in cell-free DNA (cfDNA) circulating in plasma of breast cancerpatients. DESIGN AND METHODS: Our study material consisted of: a) a pilot testing group of 27 patients with stage I-III operable breast cancer, 46 patients with verified metastasis and 37 healthy donors and b) an independent cohort of 123 consecutive stage I-III operable breast cancerpatients. Methylated and unmethylated CST6 promoter sequences were detected by using methylation-specific PCR (MSP). CST6 immunohistochemical detection was performed in 20 corresponding primary tumor tissues. RESULTS: In the pilot testing group, CST6 promoter was methylated in 8/27 (29.6%) operable breast cancerpatients, in 6/46 (13.0%) patients with verified metastasis but none of 37 healthy individuals (0%). In the independent cohort, 49/123 (39.8%) operable breast cancerpatients were found positive. During the follow up period, 25/123 (20.3%) patients relapsed and 9/123 (7.3%) died. CST6 was methylated in cfDNA of 13/25 (52%) patients that relapsed and in 3/9 (33.3%) patients that died. CONCLUSIONS:CST6 promoter is highly methylated in cfDNA of breast cancerpatients, but not in healthy individuals. CST6 promoter methylation in cfDNA, should be prospectively validated as a novel plasma tumor biomarker for breast cancer in a large cohort of breast cancerpatients.
Authors: Kala Visvanathan; MaryJo S Fackler; Zhe Zhang; Zoila A Lopez-Bujanda; Stacie C Jeter; Lori J Sokoll; Elizabeth Garrett-Mayer; Leslie M Cope; Christopher B Umbricht; David M Euhus; Andres Forero; Anna M Storniolo; Rita Nanda; Nancy U Lin; Lisa A Carey; James N Ingle; Saraswati Sukumar; Antonio C Wolff Journal: J Clin Oncol Date: 2016-11-21 Impact factor: 44.544
Authors: Theresa Benezeder; Verena Tiran; Alexandra A N Treitler; Christoph Suppan; Christopher Rossmann; Herbert Stoeger; Richard J Cote; Ram H Datar; Marija Balic; Nadia Dandachi Journal: Oncotarget Date: 2017-09-30