| Title |
Rapid progression to glioblastoma in a subset of IDH-mutated astrocytomas: a genome-wide analysis
|
|---|---|
| Published in |
Journal of Neuro-Oncology, April 2017
|
| DOI | 10.1007/s11060-017-2431-y |
| Pubmed ID | |
| Authors |
Timothy E. Richardson, Matija Snuderl, Jonathan Serrano, Matthias A. Karajannis, Adriana Heguy, Dwight Oliver, Jack M. Raisanen, Elizabeth A. Maher, Edward Pan, Samuel Barnett, Chunyu Cai, Amyn A. Habib, Robert M. Bachoo, Kimmo J. Hatanpaa |
| Abstract |
According to the recently updated World Health Organization (WHO) classification (2016), grade II-III astrocytomas are divided into IDH-wildtype and IDH-mutant groups, the latter being significantly less aggressive in terms of both progression-free and total survival. We identified a small cohort of WHO grade II-III astrocytomas that harbored the IDH1 R132H mutation, as confirmed by both immunohistochemistry and molecular sequence analysis, which nonetheless had unexpectedly rapid recurrence and subsequent progression to glioblastoma. Among these four cases, the mean time to recurrence as glioblastoma was only 16 months and the mean total survival among the three patients who have died during the follow-up was only 31 months. We hypothesized that these tumors had other, unfavorable genetic or epigenetic alterations that negated the favorable effect of the IDH mutation. We applied genome-wide profiling with a methylation array (Illumina Infinium Human Methylation 450k) to screen for genetic and epigenetic alterations in these tumors. As expected, the methylation profiles of all four tumors were found to match most closely with IDH-mutant astrocytomas. Compared with a control group of four indolent, age-similar WHO grade II-III astrocytomas, the tumors showed markedly increased levels of overall copy number changes, but no consistent specific genetic alterations were seen across all of the tumors. While most IDH-mutant WHO grade II-III astrocytomas are relatively indolent, a subset may rapidly recur and progress to glioblastoma. The precise underlying cause of the increased aggressiveness in these gliomas remains unknown, although it may be associated with increased genomic instability. |
X Demographics
The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Germany | 1 | 17% |
| Unknown | 5 | 83% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 5 | 83% |
| Practitioners (doctors, other healthcare professionals) | 1 | 17% |
Mendeley readers
The data shown below were compiled from readership statistics for 31 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 31 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 6 | 19% |
| Researcher | 3 | 10% |
| Student > Doctoral Student | 3 | 10% |
| Student > Bachelor | 3 | 10% |
| Student > Master | 3 | 10% |
| Other | 9 | 29% |
| Unknown | 4 | 13% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 12 | 39% |
| Biochemistry, Genetics and Molecular Biology | 6 | 19% |
| Neuroscience | 4 | 13% |
| Immunology and Microbiology | 1 | 3% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 3% |
| Other | 2 | 6% |
| Unknown | 5 | 16% |
Attention Score in Context
This research output has an Altmetric Attention Score of 2. 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 12 April 2018.
All research outputs
#13,547,128
of 22,965,074 outputs
Outputs from Journal of Neuro-Oncology
#1,718
of 2,985 outputs
Outputs of similar age
#158,603
of 310,294 outputs
Outputs of similar age from Journal of Neuro-Oncology
#29
of 102 outputs
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So far Altmetric has tracked 2,985 research outputs from this source. They receive a mean Attention Score of 4.2. This one is in the 41st percentile – i.e., 41% of its peers scored the same or lower than it.
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We're also able to compare this research output to 102 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 69% of its contemporaries.