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2016 ; 57
(2
): 189-97
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Wnt pathway antagonists, SFRP1, SFRP2, SOX17, and PPP2R2B, are methylated in
gliomas and SFRP1 methylation predicts shorter survival
#MMPMID26337424
Majchrzak-Celi?ska A
; S?oci?ska M
; Barciszewska AM
; Nowak S
; Baer-Dubowska W
J Appl Genet
2016[May]; 57
(2
): 189-97
PMID26337424
show ga
The deregulation of Wnt signaling is observed in various cancers, including
gliomas, and might be related to the methylation of the genes encoding
antagonists of this signaling pathway. The aim of the study was to assess the
methylation status of the promoter regions of six Wnt negative regulators and to
determine their prognostic value in clinical samples of gliomas of different
grades. The methylation of SFRP1, SFRP2, PPP2R2B, DKK1, SOX17, and DACH1 was
analyzed in 64 glioma samples using methylation-specific polymerase chain
reaction (MSP). The results were analyzed in correlation with clinicopathological
data. Promoter methylation in at least one of the analyzed genes was found in
81.3 % of the tumors. All benign tumors [grade I according to the World Health
Organization (WHO) classification] lacked the methylation of the studied genes,
whereas grade II, III, and IV tumors were, in most cases, methylation-positive.
The methylation index correlated with the patient's age. The most frequently
methylated genes were SFRP1 and SFRP2 (73.4 % and 46.9 %, respectively), followed
by SOX17 (20.3 %) and PPP2R2B (10.9 %); DKK1 and DACH1 were basically
unmethylated (1.6 %). SFRP1 methylation negatively correlated with patients'
survival time, and was significantly more frequent in older patients and those
with higher grade tumors. Overall, the results of this study indicate that
aberrant promoter methylation of Wnt pathway antagonists is common in gliomas,
which may be the possible cause of up-regulation of this signaling pathway often
observed in these tumors. Moreover, SFRP1 promoter methylation can be regarded as
a potential indicator of glioma patients' survival.
|*DNA Methylation
[MESH]
|*Wnt Signaling Pathway
[MESH]
|Adolescent
[MESH]
|Adult
[MESH]
|Aged
[MESH]
|Aged, 80 and over
[MESH]
|Female
[MESH]
|Glioma/diagnosis/*genetics
[MESH]
|Humans
[MESH]
|Intracellular Signaling Peptides and Proteins
[MESH]