title: High incidence of MGMT promoter methylation in primary glioblastomas without correlation with TP53 gene mutations.
abstract: O(6)-methylguanine DNA methyltransferase (MGMT) reduces cytotoxicity of therapeutic or environmental alkylating agents. MGMT promoter methylation has been associated with TP53 G: C to A:T transition mutations in various types of cancers, and with poor prognosis in patients who did not receive chemotherapy. Mutations of TP53 are more frequent in secondary than in primary glioblastoma, thus the expected MGMT promoter methylation was low in primary glioblastoma. Glioblastoma patients with MGMT promoter methylation showed better response to chemotherapy based on alkylating agents and longer survival than patients without MGMT methylation. We examined 32 primary glioblastomas, treated with radiotherapy and surgery, for TP53 mutation by direct sequencing and MGMT promoter methylation by methylation-specific PCR. MGMT promoter methylation and TP53 mutations were detected in 72% and 31% of primary glioblastoma, respectively. Although not statistically significant, the frequency of TP53 G:C to A:T mutations were higher in cases with (26%) than without (11%) MGMT promoter methylation (p=0.376). MGMT promoter methylation had no impact on patient survival. Our data indicate that MGMT promoter methylation occurs frequently in primary glioblastoma, but does not lead to G:C to A:T TP53 mutations, has no independent prognostic value and is not a predictive marker unless glioblastoma patients are treated with chemotherapy.
authors.affiliation: Department of Radiation Oncology, Chair of Oncology, Copernicus Memorial Hospital, Lodz, Poland.
authors.forename: Emilia
authors.initials: E
authors.lastname: Jesien-Lewandowicz
authors.forename: Dorota
authors.initials: D
authors.lastname: Jesionek-Kupnicka
authors.forename: Izabela
authors.initials: I
authors.lastname: Zawlik
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Szybka
authors.forename: Dominika
authors.initials: D
authors.lastname: Kulczycka-Wojdala
authors.forename: Piotr
authors.initials: P
authors.lastname: Rieske
authors.forename: Monika
authors.initials: M
authors.lastname: Sieruta
authors.forename: Dariusz
authors.initials: D
authors.lastname: Jaskolski
authors.forename: Waldemar
authors.initials: W
authors.lastname: Och
authors.forename: Wiesław
authors.initials: W
authors.lastname: Skowronski
authors.forename: Beata
authors.initials: B
authors.lastname: Sikorska
authors.forename: Piotr
authors.initials: P
authors.lastname: Potemski
authors.forename: Wielislaw
authors.initials: W
authors.lastname: Papierz
authors.forename: Pawel P
authors.initials: PP
authors.lastname: Liberski
authors.forename: Radzisław
authors.initials: R
authors.lastname: Kordek
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D020868:Gene Silencing; D016158:Genes, p53 / Q000235:genetics*; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D006801:Humans; D015994:Incidence; D008297:Male; D008745:Methylation; D008875:Middle Aged; D009154:Mutation; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D011401:Promoter Regions, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
chemical_list: D016159:Tumor Suppressor Protein p53; D019853:O(6)-Methylguanine-DNA Methyltransferase