| Title |
Integrated analysis of pediatric glioblastoma reveals a subset of biologically favorable tumors with associated molecular prognostic markers
|
|---|---|
| Published in |
Acta Neuropathologica, March 2015
|
| DOI | 10.1007/s00401-015-1405-4 |
| Pubmed ID | |
| Authors |
Andrey Korshunov, Marina Ryzhova, Volker Hovestadt, Sebastian Bender, Dominik Sturm, David Capper, Jochen Meyer, Daniel Schrimpf, Marcel Kool, Paul A. Northcott, Olga Zheludkova, Till Milde, Olaf Witt, Andreas E. Kulozik, Guido Reifenberger, Nada Jabado, Arie Perry, Peter Lichter, Andreas von Deimling, Stefan M. Pfister, David T. W. Jones |
| Abstract |
Pediatric glioblastoma (pedGBM) is amongst the most common malignant brain tumors of childhood and carries a dismal prognosis. In contrast to adult GBM, few molecular prognostic markers for the pediatric counterpart have been established. We, therefore, investigated the prognostic significance of genomic and epigenetic alterations through molecular analysis of 202 pedGBM (1-18 years) with comprehensive clinical annotation. Routinely prepared formalin-fixed paraffin-embedded tumor samples were assessed for genome-wide DNA methylation profiles, with known candidate genes screened for alterations via direct sequencing or FISH. Unexpectedly, a subset of histologically diagnosed GBM (n = 40, 20 %) displayed methylation profiles similar to those of either low-grade gliomas or pleomorphic xanthoastrocytomas (PXA). These tumors showed a markedly better prognosis, with molecularly PXA-like tumors frequently harboring BRAF V600E mutations and 9p21 (CDKN2A) homozygous deletion. The remaining 162 tumors with pedGBM molecular signatures comprised four subgroups: H3.3 G34-mutant (15 %), H3.3/H3.1 K27-mutant (43 %), IDH1-mutant (6 %), and H3/IDH wild-type (wt) GBM (36 %). These subgroups were associated with specific cytogenetic aberrations, MGMT methylation patterns and clinical outcomes. Analysis of follow-up data identified a set of biomarkers feasible for use in risk stratification: pedGBM with any oncogene amplification and/or K27M mutation (n = 124) represents a particularly unfavorable group, with 3-year overall survival (OS) of 5 %, whereas tumors without these markers (n = 38) define a more favorable group (3-year OS ~70 %).Combined with the lower grade-like lesions, almost 40 % of pedGBM cases had distinct molecular features associated with a more favorable outcome. This refined prognostication method for pedGBM using a molecular risk algorithm may allow for improved therapeutic choices and better planning of clinical trial stratification for this otherwise devastating disease. |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 25% |
| France | 1 | 25% |
| Unknown | 2 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 4 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 230 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 2 | <1% |
| Czechia | 1 | <1% |
| France | 1 | <1% |
| Brazil | 1 | <1% |
| Unknown | 225 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 39 | 17% |
| Researcher | 31 | 13% |
| Student > Bachelor | 23 | 10% |
| Student > Master | 21 | 9% |
| Student > Doctoral Student | 19 | 8% |
| Other | 47 | 20% |
| Unknown | 50 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 75 | 33% |
| Biochemistry, Genetics and Molecular Biology | 29 | 13% |
| Agricultural and Biological Sciences | 20 | 9% |
| Neuroscience | 16 | 7% |
| Pharmacology, Toxicology and Pharmaceutical Science | 5 | 2% |
| Other | 20 | 9% |
| Unknown | 65 | 28% |
Attention Score in Context
This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 April 2020.
All research outputs
#5,598,342
of 23,306,612 outputs
Outputs from Acta Neuropathologica
#1,204
of 2,392 outputs
Outputs of similar age
#62,522
of 259,955 outputs
Outputs of similar age from Acta Neuropathologica
#19
of 30 outputs
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