The tumoral A genotype of the MGMT rs34180180 single-nucleotide polymorphism in aggressive gliomas is associated with shorter patients’ survival

Autor: Bruno M. Costa, Jean-Louis Kemeny, Pierre Verrelle, Catherine Vaurs-Barrière, Afonso A. Pinto, Bruno Pereira, Lucie Karayan-Tapon, Mélanie Müller-Barthélémy, Franck Court, Julian Biau, Anne Fogli, Philippe Arnaud, Emmanuel Chautard, Toufic Khalil
Přispěvatelé: Service de Biochimie et Génétique Moléculaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Faculté de Médecine - Clermont-Ferrand, Université d'Auvergne - Clermont-Ferrand I (UdA), Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Laboratoire de pathologie, Service de Neurochirurgie [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], Institut National de la Transfusion Sanguine [Paris] (INTS), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service de Neurochirurgie [CHU Clermont-Ferrand], Service de Biochimie Médicale et Biologie Moléculaire [CHU Clermont-Ferrand], Génétique, Reproduction et Développement - Clermont Auvergne ( GReD ), IFR79-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Clermont Auvergne ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Université d'Auvergne - Clermont-Ferrand I ( UdA ), Génétique, reproduction et développement ( GReD ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -IFR79-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Biostat Unit, Centre Hospitalier Universitaire de Clermont-Ferrand, Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Clermont-Ferrand-Hôpital Gabriel Montpied, Institut National de la Transfusion Sanguine [Paris] ( INTS ), Centre Jean Perrin, CRLCC Jean Perrin, [et.al.], Universidade do Minho
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Adult
Male
Cancer Research
Methyltransferase
IDH1
Genotype
Single-nucleotide polymorphism
[SDV.CAN]Life Sciences [q-bio]/Cancer
Kaplan-Meier Estimate
Biology
Bioinformatics
Polymerase Chain Reaction
Polymorphism
Single Nucleotide
[ SDV.CAN ] Life Sciences [q-bio]/Cancer
03 medical and health sciences
0302 clinical medicine
[ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology
Glioma
medicine
Humans
Promoter Regions
Genetic
[ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics
DNA Modification Methylases
neoplasms
ComputingMilieux_MISCELLANEOUS
Proportional Hazards Models
Retrospective Studies
Temozolomide
Brain Neoplasms
Tumor Suppressor Proteins
Promoter
General Medicine
Methylation
DNA Methylation
Prognosis
medicine.disease
digestive system diseases
3. Good health
DNA Repair Enzymes
CpG site
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
030220 oncology & carcinogenesis
Cancer research
Female
Polymorphism
Restriction Fragment Length
030217 neurology & neurosurgery
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
medicine.drug
Zdroj: Carcinogenesis
Carcinogenesis, Oxford University Press (OUP), 2016, 37 (2), pp.169-176. ⟨10.1093/carcin/bgv251⟩
Carcinogenesis, 2016, 37 (2), pp.169-176. ⟨10.1093/carcin/bgv251⟩
Carcinogenesis, Oxford University Press (OUP), 2016, 37 (2), pp.169-176. 〈10.1093/carcin/bgv251〉
Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
ISSN: 0143-3334
1460-2180
Popis: Malignant gliomas are the most common primary brain tumors. Grade III and IV gliomas harboring wild-type IDH1/2 are the most aggressive. In addition to surgery and radiotherapy, concomitant and adjuvant chemotherapy with temozolomide (TMZ) significantly improves overall survival (OS). The methylation status of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter is predictive of TMZ response and a prognostic marker of cancer outcome. However, the promoter regions the methylation of which correlates best with survival in aggressive glioma and whether the promoter methylation status predictive value could be refined or improved by other MGMT-associated molecular markers are not precisely known. In a cohort of 87 malignant gliomas treated with radiotherapy and TMZ-based chemotherapy, we retrospectively determined the MGMT promoter methylation status, genotyped single nucleotide polymorphisms (SNPs) in the promoter region and quantified MGMT mRNA expression level. Each of these variables was correlated with each other and with the patients' OS. We found that methylation of the CpG sites within MGMT exon 1 best correlated with OS and MGMT expression levels, and confirmed MGMT methylation as a stronger independent prognostic factor compared to MGMT transcription levels. Our main finding is that the presence of only the A allele at the rs34180180 SNP in the tumor was significantly associated with shorter OS, independently of the MGMT methylation status. In conclusion, in the clinic, rs34180180 SNP genotyping could improve the prognostic value of the MGMT promoter methylation assay in patients with aggressive glioma treated with TMZ.
ARC -Fondation ARC pour la Recherche sur le Cancer(EML20120904843)
Databáze: OpenAIRE
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