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Assessing CpG island methylator phenotype, 1p/19q codeletion, and MGMT promoter methylation from epigenome-wide data in the biomarker cohort of the NOA-04 trial.
Wiestler, Benedikt; Capper, David; Hovestadt, Volker; Sill, Martin; Jones, David T W; Hartmann, Christian; Felsberg, Joerg; Platten, Michael; Feiden, Wolfgang; Keyvani, Kathy; Pfister, Stefan M; Wiestler, Otmar D; Meyermann, Richard; Reifenberger, Guido; Pietsch, Thorsten; von Deimling, Andreas; Weller, Michael; Wick, Wolfgang.
Afiliação
  • Wiestler B; Department of Neurooncology (B.W., M.P., W.W.); Department of Neuropathology (D.C., A.v.D.); Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital (S.M.P.); Clinical Cooperation Units Neurooncology (B.W., W.W.), Neuropathology (D.C, A.v.D.); Neuroimmunology and
  • Capper D; Department of Neurooncology (B.W., M.P., W.W.); Department of Neuropathology (D.C., A.v.D.); Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital (S.M.P.); Clinical Cooperation Units Neurooncology (B.W., W.W.), Neuropathology (D.C, A.v.D.); Neuroimmunology and
  • Hovestadt V; Department of Neurooncology (B.W., M.P., W.W.); Department of Neuropathology (D.C., A.v.D.); Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital (S.M.P.); Clinical Cooperation Units Neurooncology (B.W., W.W.), Neuropathology (D.C, A.v.D.); Neuroimmunology and
  • Sill M; Department of Neurooncology (B.W., M.P., W.W.); Department of Neuropathology (D.C., A.v.D.); Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital (S.M.P.); Clinical Cooperation Units Neurooncology (B.W., W.W.), Neuropathology (D.C, A.v.D.); Neuroimmunology and
  • Jones DT; Department of Neurooncology (B.W., M.P., W.W.); Department of Neuropathology (D.C., A.v.D.); Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital (S.M.P.); Clinical Cooperation Units Neurooncology (B.W., W.W.), Neuropathology (D.C, A.v.D.); Neuroimmunology and
  • Hartmann C; Department of Neurooncology (B.W., M.P., W.W.); Department of Neuropathology (D.C., A.v.D.); Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital (S.M.P.); Clinical Cooperation Units Neurooncology (B.W., W.W.), Neuropathology (D.C, A.v.D.); Neuroimmunology and
  • Felsberg J; Department of Neurooncology (B.W., M.P., W.W.); Department of Neuropathology (D.C., A.v.D.); Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital (S.M.P.); Clinical Cooperation Units Neurooncology (B.W., W.W.), Neuropathology (D.C, A.v.D.); Neuroimmunology and
  • Platten M; Department of Neurooncology (B.W., M.P., W.W.); Department of Neuropathology (D.C., A.v.D.); Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital (S.M.P.); Clinical Cooperation Units Neurooncology (B.W., W.W.), Neuropathology (D.C, A.v.D.); Neuroimmunology and
  • Feiden W; Department of Neurooncology (B.W., M.P., W.W.); Department of Neuropathology (D.C., A.v.D.); Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital (S.M.P.); Clinical Cooperation Units Neurooncology (B.W., W.W.), Neuropathology (D.C, A.v.D.); Neuroimmunology and
  • Keyvani K; Department of Neurooncology (B.W., M.P., W.W.); Department of Neuropathology (D.C., A.v.D.); Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital (S.M.P.); Clinical Cooperation Units Neurooncology (B.W., W.W.), Neuropathology (D.C, A.v.D.); Neuroimmunology and
  • Pfister SM; Department of Neurooncology (B.W., M.P., W.W.); Department of Neuropathology (D.C., A.v.D.); Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital (S.M.P.); Clinical Cooperation Units Neurooncology (B.W., W.W.), Neuropathology (D.C, A.v.D.); Neuroimmunology and
  • Wiestler OD; Department of Neurooncology (B.W., M.P., W.W.); Department of Neuropathology (D.C., A.v.D.); Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital (S.M.P.); Clinical Cooperation Units Neurooncology (B.W., W.W.), Neuropathology (D.C, A.v.D.); Neuroimmunology and
  • Meyermann R; Department of Neurooncology (B.W., M.P., W.W.); Department of Neuropathology (D.C., A.v.D.); Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital (S.M.P.); Clinical Cooperation Units Neurooncology (B.W., W.W.), Neuropathology (D.C, A.v.D.); Neuroimmunology and
  • Reifenberger G; Department of Neurooncology (B.W., M.P., W.W.); Department of Neuropathology (D.C., A.v.D.); Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital (S.M.P.); Clinical Cooperation Units Neurooncology (B.W., W.W.), Neuropathology (D.C, A.v.D.); Neuroimmunology and
  • Pietsch T; Department of Neurooncology (B.W., M.P., W.W.); Department of Neuropathology (D.C., A.v.D.); Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital (S.M.P.); Clinical Cooperation Units Neurooncology (B.W., W.W.), Neuropathology (D.C, A.v.D.); Neuroimmunology and
  • von Deimling A; Department of Neurooncology (B.W., M.P., W.W.); Department of Neuropathology (D.C., A.v.D.); Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital (S.M.P.); Clinical Cooperation Units Neurooncology (B.W., W.W.), Neuropathology (D.C, A.v.D.); Neuroimmunology and
  • Weller M; Department of Neurooncology (B.W., M.P., W.W.); Department of Neuropathology (D.C., A.v.D.); Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital (S.M.P.); Clinical Cooperation Units Neurooncology (B.W., W.W.), Neuropathology (D.C, A.v.D.); Neuroimmunology and
  • Wick W; Department of Neurooncology (B.W., M.P., W.W.); Department of Neuropathology (D.C., A.v.D.); Department of Pediatric Oncology, Hematology, and Immunology, Heidelberg University Hospital (S.M.P.); Clinical Cooperation Units Neurooncology (B.W., W.W.), Neuropathology (D.C, A.v.D.); Neuroimmunology and
Neuro Oncol ; 16(12): 1630-8, 2014 Dec.
Article em En | MEDLINE | ID: mdl-25028501
ABSTRACT

BACKGROUND:

Molecular biomarkers including isocitrate dehydrogenase 1 or 2 (IDH1/2) mutation, 1p/19q codeletion, and O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation may improve prognostication and guide treatment decisions for patients with World Health Organization (WHO) anaplastic gliomas. At present, each marker is individually tested by distinct assays. Illumina Infinium HumanMethylation450 BeadChip arrays (HM450) enable the determination of large-scale methylation profiles and genome-wide DNA copy number changes. Algorithms have been developed to detect the glioma CpG island methylator phenotype (G-CIMP) associated with IDH1/2 mutation, 1p/19q codeletion, and MGMT promoter methylation using a single assay.

METHODS:

Here, we retrospectively investigated the diagnostic and prognostic performance of these algorithms in comparison to individual marker testing and patient outcome in the biomarker cohort (n = 115 patients) of the NOA-04 trial.

RESULTS:

Concordance for IDH and 1p/19q status was very high In 92% of samples, the HM450 and reference data agreed. In discordant samples, survival analysis by Kaplan-Meier and Cox regression analyses suggested a more accurate assessment of biological phenotype by the HM450 analysis. The HM450-derived MGMT-STP27 model to calculate MGMT promoter methylation probability revealed this aberration in a significantly higher fraction of samples than conventional methylation-specific PCR, with 87 of 91 G-CIMP tumors predicted as MGMT promoter-methylated. Pyrosequencing of discordant samples confirmed the HM450 assessment in 14 of 17 cases.

CONCLUSIONS:

G-CIMP and 1p/19q codeletion are reliably detectable by HM450 analysis and are associated with prognosis in the NOA-04 trial. For MGMT, HM450 suggests promoter methylation in the vast majority of G-CIMP tumors, which is supported by pyrosequencing.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Metilação de DNA / Glioma Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2014 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Metilação de DNA / Glioma Tipo de estudo: Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2014 Tipo de documento: Article