title: TP53 promoter methylation in primary glioblastoma: relationship with TP53 mRNA and protein expression and mutation status.
abstract: Reduced expression of TP53 by promoter methylation has been reported in several neoplasms. It remains unclear whether TP53 promoter methylation is associated with reduced transcriptional and protein expression in glioblastoma (GB). The aim of our work was to study the impact of TP53 methylation and mutations on TP53 mRNA level and protein expression in 42 molecularly characterized primary GB tumors. We also evaluate the impact of all molecular alterations on the overall patient survival. The frequency of TP53 promoter methylation was found in 21.4%. To the best of our knowledge, this is the first report showing such high frequency of TP53 promoter methylation in primary GB. There was no relation between TP53 promoter methylation and TP53 mRNA level (p=0.5722) and between TP53 promoter methylation and TP53 protein expression (p=0.2045). No significant associations were found between TP53 mRNA expression and mutation of TP53 gene (p=0.9076). However, significant association between TP53 mutation and TP53 protein expression was found (p=0.0016). Our data suggest that in primary GB TP53 promoter methylation does not play a role in silencing of TP53 transcriptional and protein expression and is probably regulated by other genetic and epigenetic mechanisms associated with genes involved in the TP53 pathway.
authors: 1 Department of Tumor Pathology, Medical University of Lodz , Poland .
authors: Dorota
authors: D
authors: Jesionek-Kupnicka
authors: Malgorzata
authors: M
authors: Szybka
authors: Beata
authors: B
authors: Malachowska
authors: Wojciech
authors: W
authors: Fendler
authors: Piotr
authors: P
authors: Potemski
authors: Sylwester
authors: S
authors: Piaskowski
authors: Dariusz
authors: D
authors: Jaskolski
authors: Wielislaw
authors: W
authors: Papierz
authors: Wieslaw
authors: W
authors: Skowronski
authors: Waldemar
authors: W
authors: Och
authors: Radzislaw
authors: R
authors: Kordek
authors: Izabela
authors: I
authors: Zawlik
mesh_terms: D001483:Base Sequence; D019175:DNA Methylation; D017931:DNA Primers / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011044:Poland; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D018709:Statistics, Nonparametric; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; C000606290:SOD1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D066246:ErbB Receptors