Universität zu Köln

Tang, Qiuqiong, Holland-Letz, Tim, Slynko, Alla, Cuk, Katarina, Marme, Frederik, Schott, Sarah ORCID: 0000-0002-1714-1147, Heil, Joerg ORCID: 0000-0002-4684-9099, Qu, Bin, Golatta, Michael ORCID: 0000-0002-2605-0060, Bewerunge-Hudler, Melanie, Sutter, Christian, Surowy, Harald ORCID: 0000-0002-3595-9188, Wappenschmidt, Barbara, Schmutzler, Rita, Hoth, Markus ORCID: 0000-0001-7080-4643, Bugert, Peter, Bartram, Claus R., Sohn, Christof, Schneeweiss, Andreas, Yang, Rongxi and Burwinkel, Barbara (2016). DNA methylation array analysis identifies breast cancer associated RPTOR, MGRN1 and RAPSN hypomethylation in peripheral blood DNA. Oncotarget, 7 (39). S. 64191 - 64203. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

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Abstract

DNA methylation changes in peripheral blood DNA have been shown to be associated with solid tumors. We sought to identify methylation alterations in whole blood DNA that are associated with breast cancer (BC). Epigenome-wide DNA methylation profiling on blood DNA from BC cases and healthy controls was performed by applying Infinium HumanMethylation450K BeadChips. Promising CpG sites were selected and validated in three independent larger sample cohorts via MassARRAY EpiTyper assays. CpG sites located in three genes (cg06418238 in RPTOR, cg00736299 in MGRN1 and cg27466532 in RAPSN), which showed significant hypomethylation in BC patients compared to healthy controls in the discovery cohort (p < 1.00 x 10(-6)) were selected and successfully validated in three independent cohorts (validation I, n =211; validation II, n=378; validation III, n=520). The observed methylation differences are likely not cell-type specific, as the differences were only seen in whole blood, but not in specific sub cell-types of leucocytes. Moreover, we observed in quartile analysis that women in the lower methylation quartiles of these three loci had higher ORs than women in the higher quartiles. The combined AUC of three loci was 0.79 (95%CI 0.73-0.85) in validation cohort I, and was 0.60 (95%CI 0.54-0.66) and 0.62 (95%CI 0.57-0.67) in validation cohort II and III, respectively. Our study suggests that hypomethylation of CpG sites in RPTOR, MGRN1 and RAPSN in blood is associated with BC and might serve as blood-based marker supplements for BC if these could be verified in prospective studies.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tang, Qiuqiong UNSPECIFIED UNSPECIFIED UNSPECIFIED Holland-Letz, Tim UNSPECIFIED UNSPECIFIED UNSPECIFIED Slynko, Alla UNSPECIFIED UNSPECIFIED UNSPECIFIED Cuk, Katarina UNSPECIFIED UNSPECIFIED UNSPECIFIED Marme, Frederik UNSPECIFIED UNSPECIFIED UNSPECIFIED Schott, Sarah UNSPECIFIED orcid.org/0000-0002-1714-1147 UNSPECIFIED Heil, Joerg UNSPECIFIED orcid.org/0000-0002-4684-9099 UNSPECIFIED Qu, Bin UNSPECIFIED UNSPECIFIED UNSPECIFIED Golatta, Michael UNSPECIFIED orcid.org/0000-0002-2605-0060 UNSPECIFIED Bewerunge-Hudler, Melanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Sutter, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Surowy, Harald UNSPECIFIED orcid.org/0000-0002-3595-9188 UNSPECIFIED Wappenschmidt, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmutzler, Rita UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoth, Markus UNSPECIFIED orcid.org/0000-0001-7080-4643 UNSPECIFIED Bugert, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Bartram, Claus R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sohn, Christof UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneeweiss, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Yang, Rongxi UNSPECIFIED UNSPECIFIED UNSPECIFIED Burwinkel, Barbara UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-262004
DOI:	10.18632/oncotarget.11640
Journal or Publication Title:	Oncotarget
Volume:	7
Number:	39
Page Range:	S. 64191 - 64203
Date:	2016
Publisher:	IMPACT JOURNALS LLC
Place of Publication:	ORCHARD PARK
ISSN:	1949-2553
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CLINICAL-PRACTICE GUIDELINES; BRCA1 PROMOTER METHYLATION; WIDE ASSOCIATION; TUMOR-MARKER; WHOLE-BLOOD; RISK; BIOMARKER; RECOMMENDATIONS; SUSCEPTIBILITY; MAMMOGRAPHY Multiple languages Oncology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26200