Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.11640
Title: DNA methylation array analysis identifies breast cancer associated RPTOR, MGRN1 and RAPSN hypomethylation in peripheral blood DNA
Authors: Tang, Q
Holland-Letz, T
Slynko, A
Cuk, K
Marme, F
Schott, S
Heil, J
Qu, B 
Golatta, M
Bewerunge-Hudler, M
Sutter, C
Surowy, H
Wappenschmidt, B
Schmutzler, R
Hoth, M
Bugert, P
Bartram, C.R
Sohn, C
Schneeweiss, A
Yang, R
Burwinkel, B
Keywords: adult
area under the curve
Article
breast cancer
case control study
cell specificity
cohort analysis
controlled study
CpG island
DNA methylation
epigenetics
female
gene
gene locus
genetic association
human
human cell
leukocyte
major clinical study
MGRN1 gene
RAPSN gene
receiver operating characteristic
RPTOR gene
sensitivity and specificity
validation study
aged
blood
breast tumor
comparative study
DNA microarray
gene expression profiling
genetic epigenesis
genetic predisposition
genetics
middle aged
odds ratio
pathology
predictive value
procedures
reproducibility
retrospective study
risk factor
statistical model
circulating tumor DNA
MGRN1 protein, human
muscle protein
peripheral membrane protein 43K
regulatory associated protein of mTOR
RPTOR protein, human
tumor marker
ubiquitin protein ligase
Adult
Aged
Area Under Curve
Biomarkers, Tumor
Breast Neoplasms
Circulating Tumor DNA
CpG Islands
DNA Methylation
Epigenesis, Genetic
Female
Gene Expression Profiling
Genetic Predisposition to Disease
Humans
Logistic Models
Middle Aged
Muscle Proteins
Odds Ratio
Oligonucleotide Array Sequence Analysis
Predictive Value of Tests
Regulatory-Associated Protein of mTOR
Reproducibility of Results
Retrospective Studies
Risk Factors
ROC Curve
Ubiquitin-Protein Ligases
Issue Date: 2016
Publisher: Impact Journals LLC
Citation: Tang, Q, Holland-Letz, T, Slynko, A, Cuk, K, Marme, F, Schott, S, Heil, J, Qu, B, Golatta, M, Bewerunge-Hudler, M, Sutter, C, Surowy, H, Wappenschmidt, B, Schmutzler, R, Hoth, M, Bugert, P, Bartram, C.R, Sohn, C, Schneeweiss, A, Yang, R, Burwinkel, B (2016). DNA methylation array analysis identifies breast cancer associated RPTOR, MGRN1 and RAPSN hypomethylation in peripheral blood DNA. Oncotarget 7 (39) : 64191-64202. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.11640
Rights: Attribution 4.0 International
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.
Source Title: Oncotarget
URI: https://scholarbank.nus.edu.sg/handle/10635/180382
ISSN: 1949-2553
DOI: 10.18632/oncotarget.11640
Rights: Attribution 4.0 International
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