| Title |
H3-/IDH-wild type pediatric glioblastoma is comprised of molecularly and prognostically distinct subtypes with associated oncogenic drivers
|
|---|---|
| Published in |
Acta Neuropathologica, April 2017
|
| DOI | 10.1007/s00401-017-1710-1 |
| Pubmed ID | |
| Authors |
Andrey Korshunov, Daniel Schrimpf, Marina Ryzhova, Dominik Sturm, Lukas Chavez, Volker Hovestadt, Tanvi Sharma, Antje Habel, Anna Burford, Chris Jones, Olga Zheludkova, Ella Kumirova, Christof M. Kramm, Andrey Golanov, David Capper, Andreas von Deimling, Stefan M. Pfister, David T. W. Jones |
| Abstract |
Pediatric glioblastoma (pedGBM) is an extremely aggressive pediatric brain tumor, accounting for ~6% of all central nervous system neoplasms in children. Approximately half of pedGBM harbor recurrent somatic mutations in histone 3 variants or, infrequently, IDH1/2. The remaining subset of pedGBM is highly heterogeneous, and displays a variety of genomic and epigenetic features. In the current study, we aimed to further stratify an H3-/IDH-wild type (wt) pedGBM cohort assessed through genome-wide molecular profiling. As a result, we identified three molecular subtypes of these tumors, differing in their genomic and epigenetic signatures as well as in their clinical behavior. We designated these subtypes 'pedGBM_MYCN' (enriched for MYCN amplification), 'pedGBM_RTK1' (enriched for PDGFRA amplification) and 'pedGBM_RTK2' (enriched for EGFR amplification). These molecular subtypes were associated with significantly different outcomes, i.e. pedGBM_RTK2 tumors show a significantly longer survival time (median OS 44 months), pedGBM_MYCN display extremely poor outcomes (median OS 14 months), and pedGBM_RTK1 tumors harbor an intermediate prognosis. In addition, the various molecular subtypes of H3-/IDH-wt pedGBM were clearly distinguishable from their adult counterparts, underlining their biological distinctiveness. In conclusion, our study demonstrates significant molecular heterogeneity of H3-/IDH-wt pedGBM in terms of DNA methylation and cytogenetic alterations. The recognition of three molecular subtypes of H3-/IDH-wt pedGBM further revealed close correlations with biological parameters and clinical outcomes and may therefore, be predictive of response to standard treatment protocols, but could also be useful for stratification for novel, molecularly based therapies. |
X Demographics
The data shown below were collected from the profiles of 9 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 Kingdom | 1 | 11% |
| Germany | 1 | 11% |
| Portugal | 1 | 11% |
| France | 1 | 11% |
| Unknown | 5 | 56% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 8 | 89% |
| Practitioners (doctors, other healthcare professionals) | 1 | 11% |
Mendeley readers
The data shown below were compiled from readership statistics for 126 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | <1% |
| Unknown | 125 | 99% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 20 | 16% |
| Researcher | 17 | 13% |
| Student > Master | 14 | 11% |
| Student > Doctoral Student | 12 | 10% |
| Student > Bachelor | 9 | 7% |
| Other | 25 | 20% |
| Unknown | 29 | 23% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 32 | 25% |
| Biochemistry, Genetics and Molecular Biology | 19 | 15% |
| Agricultural and Biological Sciences | 12 | 10% |
| Neuroscience | 9 | 7% |
| Unspecified | 4 | 3% |
| Other | 13 | 10% |
| Unknown | 37 | 29% |
Attention Score in Context
This research output has an Altmetric Attention Score of 5. 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 08 February 2018.
All research outputs
#6,282,360
of 23,577,654 outputs
Outputs from Acta Neuropathologica
#1,279
of 2,407 outputs
Outputs of similar age
#98,519
of 311,109 outputs
Outputs of similar age from Acta Neuropathologica
#32
of 38 outputs
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