Gliomatosis cerebri: no evidence for a separate brain tumor entity (vol 131, pg 309, 2016)

被引：5

作者：

Herrlinger, Ulrich ^{[1
]}

Jones, David T. W. ^{[2
,3
]}

Glas, Martin ^{[1
,4
]}

Hattingen, Elke ^{[5
]}

Gramatzki, Dorothee ^{[6
]}

Stuplich, Moritz ^{[1
]}

Felsberg, Joerg ^{[7
]}

Baehr, Oliver ^{[15
]}

Gielen, Gerrit H. ^{[8
]}

Simon, Matthias ^{[9
]}

Wiewrodt, Dorothee ^{[16
]}

Schabet, Martin ^{[17
]}

Hovestadt, Volker ^{[3
,10
]}

Capper, David ^{[3
,11
,12
]}

Steinbach, Joachim P. ^{[15
]}

von Deimling, Andreas ^{[3
,11
,12
]}

Lichter, Peter ^{[3
,10
]}

Pfister, Stefan M. ^{[2
,3
,13
]}

Weller, Michael ^{[6
]}

Reifenberger, Guido ^{[7
,14
]}

机构：

[1] Univ Med Ctr Bonn, Dept Neurol, Div Neurooncol, Sigmund Freud Str 25, D-53127 Bonn, Germany

[2] German Canc Res Ctr, Div Pediat Neurooncol, Heidelberg, Germany

[3] Core Ctr Heidelberg, German Canc Consortium DKTK, Heidelberg, Germany

[4] Univ Bonn, Life & Brain Ctr, Inst Reconstruct Neurobiol, Bonn, Germany

[5] Univ Bonn, Dept Radiol, Div Neuroradiol, Bonn, Germany

[6] Univ Zurich, Dept Neurol, Zurich, Switzerland

[7] Univ Dusseldorf, Dept Neuropathol, Dusseldorf, Germany

[8] Univ Bonn, Dept Neuropathol, Bonn, Germany

[9] Univ Bonn, Dept Neurosurg, Bonn, Germany

[10] German Canc Res Ctr, Div Mol Genet, Heidelberg, Germany

[11] German Canc Res Ctr DKFZ Heidelberg, Clin Cooperat Unit Neuropathol, Heidelberg, Germany

[12] Heidelberg Univ, Dept Neuropathol, Heidelberg, Germany

[13] Heidelberg Univ, Dept Pediat Oncol Hematol & Immunol, Heidelberg, Germany

[14] German Canc Res Ctr DKFZ Heidelberg, German Canc Consortium DKTK, Partner Site, Dusseldorf, Germany

[15] Goethe Univ Frankfurt, Dr Senckenberg Inst Neurooncol, D-60054 Frankfurt, Germany

[16] Univ Munster, Dept Neurosurg, D-48149 Munster, Germany

[17] Klinikum Ludwigsburg, Dept Neurol, Ludwigsburg, Germany

来源：

ACTA NEUROPATHOLOGICA | 2016年 / 131卷 / 02期

关键词：

DNA methylation profiles; Genomic aberrations; Gliomatosis cerebri; IDH1; mutation; MGMT promoter methylation; Molecular classification;

D O I：

10.1007/s00401-015-1523-z

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Gliomatosis cerebri (GC) is presently considered a distinct astrocytic glioma entity according to the WHO classification for CNS tumors. It is characterized by widespread, typically bilateral infiltration of the brain involving three or more lobes. Genetic studies of GC have to date been restricted to the analysis of individual glioma-associated genes, which revealed mutations in the isocitrate dehydrogenase 1 (IDH1) and tumor protein p53 (TP53) genes in subsets of patients. Here, we report on a genome-wide analysis of DNA methylation and copy number aberrations in 25 GC patients. Results were compared with those obtained for 105 patients with various types of conventional, i.e., non-GC gliomas including diffuse astrocytic gliomas, oligodendrogliomas and glioblastomas. In addition, we assessed the prognostic role of methylation profiles and recurrent DNA copy number aberrations in GC patients. Our data reveal that the methylation profiles in 23 of the 25 GC tumors corresponded to either IDH mutant astrocytoma (n = 6), IDH mutant and 1p/19q codeleted oligodendroglioma (n = 5), or IDH wild-type glioblastoma including various molecular subgroups, i.e., H3F3A-G34 mutant (n = 1), receptor tyrosine kinase 1 (RTK1, n = 4), receptor tyrosine kinase 2 (classic) (RTK2, n = 2) or mesenchymal (n = 5) glioblastoma groups. Two tumors showed methylation profiles of normal brain tissue due to low tumor cell content. While histological grading (WHO grade IV vs. WHO grade II and III) was not prognostic, the molecular classification as classic/RTK2 or mesenchymal glioblastoma was associated with worse overall survival. Multivariate Cox regression analysis revealed MGMT promoter methylation as a positive prognostic factor. Taken together, DNA-based large-scale molecular profiling indicates that GC comprises a genetically and epigenetically heterogeneous group of diffuse gliomas that carry DNA methylation and copy number profiles closely matching the common molecularly defined glioma entities. These data support the removal of GC as a distinct glioma entity in the upcoming revision of the WHO classification.

引用

页码：321 / 322

页数：2