The MGMT promoter SNP rs16906252 is a risk factor for MGMT methylation in glioblastoma and is predictive of response to temozolomide.

Abstract:

BACKGROUND:Promoter methylation of O(6)-methylguanine-DNA methyltransferase (MGMT) is an important predictive biomarker in glioblastoma. The T variant of the MGMT promoter-enhancer single nucleotide polymorphism (SNP; rs16906252) has been associated with the presence of MGMT promoter methylation in other cancers. We examined the association of the T allele of rs16906252 with glioblastoma development, tumor MGMT methylation, MGMT protein expression, and survival outcomes. METHODS:Two independent temozolomide-treated glioblastoma cohorts-one Australian (Australian Genomics and Clinical Outcomes of Glioma, n = 163) and the other American (University of California Los Angeles/Kaiser Permanente Los Angeles, n = 159)-were studied. Allelic bisulphite sequencing was used to determine if methylation was specific to the T allele. Additionally, we compared the incidence of the T allele between glioblastoma cases and matched controls to assess whether it was a risk factor for developing MGMT methylated glioblastoma. RESULTS:Carriage of the T allele of the rs16906252 SNP was associated with both MGMT methylation and low MGMT protein expression and predicted significantly longer survival in temozolomide-treated patients with both MGMT methylated and nonmethylated glioblastoma. Methylation was linked to the T allele, inferring that the T variant plays a key role in the acquisition of MGMT methylation. Carriage of the T allele was associated with a significantly elevated risk of developing glioblastoma (adjusted odds ratio, 1.96; P = .013), increasing further when glioblastoma was classified by the presence of MGMT methylation (adjusted odds ratio, 2.86; P = .001). CONCLUSIONS:The T allele of the rs16906252 SNP is a key determinant in the acquisition of MGMT methylation in glioblastoma. Temozolomide-treated patients with the rs16906252 T genotype have better survival, irrespective of tumor methylation status.

journal_name

Neuro Oncol

journal_title

Neuro-oncology

authors

Rapkins RW,Wang F,Nguyen HN,Cloughesy TF,Lai A,Ha W,Nowak AK,Hitchins MP,McDonald KL

doi

10.1093/neuonc/nov064

subject

Has Abstract

pub_date

2015-12-01 00:00:00

pages

1589-98

issue

12

eissn

1522-8517

issn

1523-5866

pii

nov064

journal_volume

17

pub_type

杂志文章
  • BRD4 as a therapeutic target for nonfunctioning and growth hormone pituitary adenoma.

    abstract:BACKGROUND:Nonfunctioning pituitary adenoma (NFPA) and growth hormone pituitary adenoma (GHPA) are major subtypes of pituitary adenomas (PAs). The primary treatment is surgical resection. However, radical excision remains challenging, and few effective medical therapies are available. It is urgent to find novel targets...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/noaa084

    authors: Shi C,Ye Z,Han J,Ye X,Lu W,Ji C,Li Z,Ma Z,Zhang Q,Zhang Y,He W,Chen Z,Cao X,Shou X,Zhou X,Wang Y,Zhang Z,Li Y,Ye H,He M,Chen H,Cheng H,Sun J,Cai J,Huang C,Ye F,Luo C,Zhou B,Ding H,Zhao Y

    更新日期:2020-08-17 00:00:00

  • Akt2 and Akt3 play a pivotal role in malignant gliomas.

    abstract::Akt, one of the major downstream effectors of phosphatidylinositol 3-kinase, is hyper-expressed and activated in a variety of cancers including glioblastoma. However, the expression profiles of the Akt isoforms Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma and their functional roles in malignant glioma are not well u...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nop026

    authors: Mure H,Matsuzaki K,Kitazato KT,Mizobuchi Y,Kuwayama K,Kageji T,Nagahiro S

    更新日期:2010-03-01 00:00:00

  • Invasion and proliferation kinetics in enhancing gliomas predict IDH1 mutation status.

    abstract:BACKGROUND:Glioblastomas with a specific mutation in the isocitrate dehydrogenase 1 (IDH1) gene have a better prognosis than gliomas with wild-type IDH1. METHODS:Here we compare the IDH1 mutational status in 172 contrast-enhancing glioma patients with the invasion profile generated by a patient-specific mathematical m...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nou027

    authors: Baldock AL,Yagle K,Born DE,Ahn S,Trister AD,Neal M,Johnston SK,Bridge CA,Basanta D,Scott J,Malone H,Sonabend AM,Canoll P,Mrugala MM,Rockhill JK,Rockne RC,Swanson KR

    更新日期:2014-06-01 00:00:00

  • Prognostic significance of the aggregative perivascular growth pattern of tumor cells in primary central nervous system diffuse large B-cell lymphoma.

    abstract:BACKGROUND:Primary central nervous system lymphomas, predominantly diffuse large B-cell lymphomas (PCNS-DLBCL), are aggressive malignancies, and no histopathological variables with independent prognostic value are currently available. The aim of this study is to determine the prognostic value of histopathological varia...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/not012

    authors: He M,Zuo C,Wang J,Liu J,Jiao B,Zheng J,Cai Z

    更新日期:2013-06-01 00:00:00

  • Memory in low-grade glioma patients treated with radiotherapy or Temozolomide. A correlative analysis of EORTC study 22033-26033.

    abstract:BACKGROUND:EORTC study 22033-26033 showed no difference in progression-free survival between high-risk low-grade glioma receiving either radiotherapy (RT) or Temozolomide (TMZ) chemotherapy alone as primary treatment. Considering the potential long-term deleterious impact of radiotherapy on memory functioning, this stu...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/noaa252

    authors: Klein M,Drijver AJ,van den Bent MJ,Bromberg JC,Hoang-Xuan K,Taphoorn MJB,Reijneveld JC,Ben Hassel M,Vauleon E,Eekers DBP,Tzuk-Shina T,Lucas A,Freixa SV,Golfinopoulos V,Gorlia T,Hottinger AF,Stupp R,Baumert BG

    更新日期:2020-11-01 00:00:00

  • Reactive species balance via GTP cyclohydrolase I regulates glioblastoma growth and tumor initiating cell maintenance.

    abstract:Background:Depending on the level, differentiation state, and tumor stage, reactive nitrogen and oxygen species inhibit or increase cancer growth and tumor initiating cell maintenance. The rate-limiting enzyme in a pathway that can regulate reactive species production but has not been thoroughly investigated in gliobla...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/noy012

    authors: Tran AN,Walker K,Harrison DG,Chen W,Mobley J,Hocevar L,Hackney JR,Sedaka RS,Pollock JS,Goldberg MS,Hambardzumyan D,Cooper SJ,Gillespie Y,Hjelmeland AB

    更新日期:2018-07-05 00:00:00

  • Imaging of brain and brain tumor specimens by time-resolved multiphoton excitation microscopy ex vivo.

    abstract::Multiphoton excitation fluorescent microscopy is a laser-based technology that allows subcellular resolution of native tissues in situ. We have recently applied this technology to the structural and photochemical imaging of cultured glioma cells and experimental gliomas ex vivo. We demonstrated that high microanatomic...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1215/15228517-2006-034

    authors: Kantelhardt SR,Leppert J,Krajewski J,Petkus N,Reusche E,Tronnier VM,Hüttmann G,Giese A

    更新日期:2007-04-01 00:00:00

  • Survivorship care planning and implementation in neuro-oncology.

    abstract::Survivorship has become a significant topic within oncologic care. The tools and means by which the provision of survivorship care can be implemented and delivered are in development and are the focus of significant research oncology-wide. These tools and methods include innovations of survivorship care delivery, surv...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/noy110

    authors: Leeper H,Milbury K

    更新日期:2018-11-09 00:00:00

  • Radiation-induced cognitive toxicity: pathophysiology and interventions to reduce toxicity in adults.

    abstract::Radiotherapy is ubiquitous in the treatment of patients with both primary brain tumors as well as disease which is metastatic to the brain. This therapy is not without cost, however, as cognitive decline is frequently associated with cranial radiation, particularly with whole brain radiotherapy (WBRT). The precise mec...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,评审

    doi:10.1093/neuonc/nox195

    authors: Wilke C,Grosshans D,Duman J,Brown P,Li J

    更新日期:2018-04-09 00:00:00

  • The L84F polymorphic variant of human O6-methylguanine-DNA methyltransferase alters stability in U87MG glioma cells but not temozolomide sensitivity.

    abstract::First-line therapy for patients with glioblastoma multiforme includes treatment with radiation and temozolomide (TMZ), an oral DNA alkylating chemotherapy. Sensitivity of glioma cells to TMZ is dependent on the level of cellular O(6)-methylguanine-DNA methyltransferase (MGMT) repair activity. Several common coding-reg...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1215/15228517-2008-080

    authors: Remington M,Chtchetinin J,Ancheta K,Nghiemphu PL,Cloughesy T,Lai A

    更新日期:2009-02-01 00:00:00

  • Detection of glioblastoma response to temozolomide combined with bevacizumab based on μMRI and μPET imaging reveals [18F]-fluoro-L-thymidine as an early and robust predictive marker for treatment efficacy.

    abstract::The individualized care of glioma patients ought to benefit from imaging biomarkers as precocious predictors of therapeutic efficacy. Contrast enhanced MRI and [(18)F]-fluorodeoxyglucose (FDG)-PET are routinely used in clinical settings; their ability to forecast the therapeutic response is controversial. The objectiv...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nos260

    authors: Corroyer-Dulmont A,Pérès EA,Petit E,Guillamo JS,Varoqueaux N,Roussel S,Toutain J,Divoux D,MacKenzie ET,Delamare J,Ibazizène M,Lecocq M,Jacobs AH,Barré L,Bernaudin M,Valable S

    更新日期:2013-01-01 00:00:00

  • A new patient-derived orthotopic malignant meningioma model treated with oncolytic herpes simplex virus.

    abstract:BACKGROUND:Higher-grade meningiomas (HGMs; World Health Organization grades II and III) pose a clinical problem due to high recurrence rates and the absence of effective therapy. Preclinical development of novel therapeutics requires a disease model that recapitulates the genotype and phenotype of patient HGM. Oncolyti...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/now031

    authors: Nigim F,Esaki S,Hood M,Lelic N,James MF,Ramesh V,Stemmer-Rachamimov A,Cahill DP,Brastianos PK,Rabkin SD,Martuza RL,Wakimoto H

    更新日期:2016-09-01 00:00:00

  • Global incidence of malignant brain and other central nervous system tumors by histology, 2003-2007.

    abstract:Background:Previous reports have shown that overall incidence of malignant brain and other central nervous system (CNS) tumors varied significantly by country. The aim of this study was to estimate histology-specific incidence rates by global region and assess incidence variation by histology and age. Methods:Using da...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nox091

    authors: Leece R,Xu J,Ostrom QT,Chen Y,Kruchko C,Barnholtz-Sloan JS

    更新日期:2017-10-19 00:00:00

  • Functional analysis of a novel glioma antigen, EFTUD1.

    abstract:BACKGROUND:A cDNA library made from 2 glioma cell lines, U87MG and T98G, was screened by serological identification of antigens by recombinant cDNA expression (SEREX) using serum from a glioblastoma patient. Elongation factor Tu GTP binding domain containing protein 1 (EFTUD1), which is required for ribosome biogenesis...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nou132

    authors: Saito K,Iizuka Y,Ohta S,Takahashi S,Nakamura K,Saya H,Yoshida K,Kawakami Y,Toda M

    更新日期:2014-12-01 00:00:00

  • The role of pericytes in blood-vessel formation and maintenance.

    abstract::Blood vessels are composed of two interacting cell types. Endothelial cells form the inner lining of the vessel wall, and perivascular cells--referred to as pericytes, vascular smooth muscle cells or mural cells--envelop the surface of the vascular tube. Over the last decades, studies of blood vessels have concentrate...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,评审

    doi:10.1215/S1152851705000232

    authors: Bergers G,Song S

    更新日期:2005-10-01 00:00:00

  • Biology and management of ependymomas.

    abstract::Ependymomas are rare primary tumors of the central nervous system in children and adults that comprise histologically similar but genetically distinct subgroups. The tumor biology is typically more associated with the site of origin rather than being age-specific. Genetically distinct subgroups have been identified by...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,评审

    doi:10.1093/neuonc/now016

    authors: Wu J,Armstrong TS,Gilbert MR

    更新日期:2016-07-01 00:00:00

  • Late relapse in primary central nervous system lymphoma: clonal persistence.

    abstract::Recurrence of primary central nervous system lymphoma (PCNSL) after initial diagnosis and treatment occurs within 2 years in most patients, and relapse after 5 years is rare. We evaluated late relapse in our PCNSL population. We identified 10 patients from our database of 378 patients (268 achieved a complete response...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nor014

    authors: Nayak L,Hedvat C,Rosenblum MK,Abrey LE,DeAngelis LM

    更新日期:2011-05-01 00:00:00

  • Association between hippocampal dose and memory in survivors of childhood or adolescent low-grade glioma: a 10-year neurocognitive longitudinal study.

    abstract:BACKGROUND:Hippocampal avoidance has been suggested as a strategy to reduce short-term memory decline in adults receiving whole-brain radiation therapy (RT). The purpose of this study was to determine whether the hippocampal dose in children and adolescents undergoing RT for low-grade glioma was associated with memory,...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/noz068

    authors: Acharya S,Wu S,Ashford JM,Tinkle CL,Lucas JT,Qaddoumi I,Gajjar A,Krasin MJ,Conklin HM,Merchant TE

    更新日期:2019-09-06 00:00:00

  • COMT, BDNF, and DTNBP1 polymorphisms and cognitive functions in patients with brain tumors.

    abstract:BACKGROUND:Cognitive dysfunction is common among patients with brain tumors and can be associated with the disease and treatment with radiotherapy and chemotherapy. However, little is known about genetic risk factors that may moderate the vulnerability for developing cognitive dysfunction. In this study, we examined th...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/now057

    authors: Correa DD,Satagopan J,Cheung K,Arora AK,Kryza-Lacombe M,Xu Y,Karimi S,Lyo J,DeAngelis LM,Orlow I

    更新日期:2016-10-01 00:00:00

  • Treatment of progressive metastatic glomus jugulare tumor (paraganglioma) with gemcitabine.

    abstract::Paragangliomas are rare tumors of the paraganglia composed of specialized neural crest cells arising in association with sympathetic ganglia. Here we report a case of progressive, metastatic paraganglioma (glomus jugulare tumor) responsive to single agent gemcitabine. In addition, a brief review of chemotherapy for pa...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/2.3.190

    authors: Pipas JM,Krywicki RF

    更新日期:2000-07-01 00:00:00

  • Phase II preradiation R115777 (tipifarnib) in newly diagnosed GBM with residual enhancing disease.

    abstract::Glioblastoma multiforme (GBM) is a lethal primary malignant brain tumor in adults. R115777 (tipifarnib) is an oral agent with antiproliferative effects, being a potent and selective inhibitor of farnesyltransferase. This multicenter, open-label phase II study was designed to evaluate the efficacy and safety of R115777...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,多中心研究

    doi:10.1215/15228517-2008-070

    authors: Lustig R,Mikkelsen T,Lesser G,Grossman S,Ye X,Desideri S,Fisher J,Wright J,New Approaches to Brain Tumor Therapy CNS Consortium.

    更新日期:2008-12-01 00:00:00

  • Racial differences in primary central nervous system lymphoma incidence and survival rates.

    abstract::To determine racial and ethnic differences in incidence and survival in patients with primary central nervous system lymphoma (PCNSL), NCI Surveillance, Epidemiology, and End Results (SEER) program data from 1992 to 2002 were queried. Data were substratified by age (20-49 years vs. 50 or above) and race (White, Black,...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1215/15228517-2008-103

    authors: Pulido JS,Vierkant RA,Olson JE,Abrey L,Schiff D,O'Neill BP

    更新日期:2009-06-01 00:00:00

  • An epidemiology report for primary central nervous system tumors in adolescents and young adults: a nationwide population-based study in France, 2008-2013.

    abstract:BACKGROUND:Primary central nervous system tumors (PCNST) among adolescents and young adults (AYA, 15-39 y) have rarely been reported. We present a nationwide report of PCNST histologically confirmed in the French AYA population between 2008 and 2013. METHODS:Patients were identified through the French Brain Tumor Data...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/noz227

    authors: Ng S,Zouaoui S,Bessaoud F,Rigau V,Roux A,Darlix A,Bauchet F,Mathieu-Daudé H,Trétarre B,Figarella-Branger D,Pallud J,Frappaz D,Roujeau T,Bauchet L

    更新日期:2020-06-09 00:00:00

  • Serum angiogenic profile of patients with glioblastoma identifies distinct tumor subtypes and shows that TIMP-1 is a prognostic factor.

    abstract::Angiogenesis plays a key role in glioblastoma biology and antiangiogenic agents are under clinical investigation with promising results. However, the angiogenic profiles of patients with glioblastoma and their clinical significance are not well understood. Here we characterize the serum angiogenic profile of patients ...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/noq170

    authors: Crocker M,Ashley S,Giddings I,Petrik V,Hardcastle A,Aherne W,Pearson A,Bell BA,Zacharoulis S,Papadopoulos MC

    更新日期:2011-01-01 00:00:00

  • DNA hypermethylation profiles associated with glioma subtypes and EZH2 and IGFBP2 mRNA expression.

    abstract::We explored the associations of aberrant DNA methylation patterns in 12 candidate genes with adult glioma subtype, patient survival, and gene expression of enhancer of zeste human homolog 2 (EZH2) and insulin-like growth factor-binding protein 2 (IGFBP2). We analyzed 154 primary glioma tumors (37 astrocytoma II and II...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/noq190

    authors: Zheng S,Houseman EA,Morrison Z,Wrensch MR,Patoka JS,Ramos C,Haas-Kogan DA,McBride S,Marsit CJ,Christensen BC,Nelson HH,Stokoe D,Wiemels JL,Chang SM,Prados MD,Tihan T,Vandenberg SR,Kelsey KT,Berger MS,Wiencke JK

    更新日期:2011-03-01 00:00:00

  • Low-dose fractionated radiotherapy and concomitant chemotherapy in glioblastoma multiforme with poor prognosis: a feasibility study.

    abstract::We explored the feasibility of concurrent palliative chemotherapy and low-dose fractionated radiotherapy (LD-FRT) in glioblastoma multiforme (GBM). Patients with recurrent/progressive GBM at least 3 months after the end of primary radiotherapy received 0.3 Gy twice daily with cisplatin and fotemustine if progressing o...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1093/neuonc/nor173

    authors: Balducci M,Chiesa S,Diletto B,D'Agostino GR,Mangiola A,Manfrida S,Mantini G,Albanese A,Fiorentino A,Frascino V,De Bari B,Micciche' F,De Rose F,Morganti AG,Anile C,Valentini V

    更新日期:2012-01-01 00:00:00

  • Peripheral neuropathies from chemotherapeutics and targeted agents: diagnosis, treatment, and prevention.

    abstract::Peripheral neuropathies induced by chemotherapy (CIPN) are an increasingly frequent problem. Contrary to hematologic adverse effects, which can be treated with hematopoetic growth factors, neither prophylaxis nor specific treatment is available, and only symptomatic treatment can be offered. Neurotoxic drugs are becom...

    journal_title:Neuro-oncology

    pub_type: 杂志文章,评审

    doi:10.1093/neuonc/nos203

    authors: Grisold W,Cavaletti G,Windebank AJ

    更新日期:2012-09-01 00:00:00

  • Motexafin gadolinium and involved field radiation therapy for intrinsic pontine glioma of childhood: a Children's Oncology Group phase I study.

    abstract::The purpose of this study was to determine the dose-limiting toxicities, maximum tolerated dose, pharmacokinetics, and intratumor and brain distribution of motexafin gadolinium (MGd) with involved field radiation therapy in children with newly diagnosed intrinsic pontine gliomas. MGd was administered as a 5-min intrav...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1215/15228517-2008-043

    authors: Bradley KA,Pollack IF,Reid JM,Adamson PC,Ames MM,Vezina G,Blaney S,Ivy P,Zhou T,Krailo M,Reaman G,Mehta MP,Children's Oncology Group.

    更新日期:2008-10-01 00:00:00

  • Role of a second chemotherapy in recurrent malignant glioma patients who progress on bevacizumab.

    abstract::Bevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor (VEGF) that has efficacy in recurrent malignant gliomas, particularly in combination with irinotecan. However, responses are rarely durable. Continuation of bevacizumab in combination with another chemotherapeutic agent may demon...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1215/15228517-2009-006

    authors: Quant EC,Norden AD,Drappatz J,Muzikansky A,Doherty L,Lafrankie D,Ciampa A,Kesari S,Wen PY

    更新日期:2009-10-01 00:00:00

  • High failure rate in spinal ependymomas with long-term follow-up.

    abstract::Data on spinal ependymomas are sparse, and prognostic factors remain controversial. The primary aim of this study is to review a historical cohort, with large patient numbers and long follow-up, and provide estimates of time to progression (TTP) and survival after progression. As a secondary aim, we assess the effects...

    journal_title:Neuro-oncology

    pub_type: 杂志文章

    doi:10.1215/S1152851704001231

    authors: Gomez DR,Missett BT,Wara WM,Lamborn KR,Prados MD,Chang S,Berger MS,Haas-Kogan DA

    更新日期:2005-07-01 00:00:00