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DNA methylation array analysis identifies breast cancer associated RPTOR, MGRN1
and RAPSN hypomethylation in peripheral blood DNA
#MMPMID27577081
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 CR
; Sohn C
; Schneeweiss A
; Yang R
; Burwinkel B
Oncotarget
2016[Sep]; 7
(39
): 64191-64202
PMID27577081
show ga
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.
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