| Title |
Altered global histone-trimethylation code and H3F3A-ATRX mutation in pediatric GBM
|
|---|---|
| Published in |
Journal of Neuro-Oncology, December 2014
|
| DOI | 10.1007/s11060-014-1675-z |
| Pubmed ID | |
| Authors |
Pankaj Pathak, Prerana Jha, Suvendu Purkait, Vikas Sharma, Vaishali Suri, Mehar C. Sharma, Mohammed Faruq, Ashish Suri, Chitra Sarkar |
| Abstract |
Mutations in H3.3-ATRX-DAXX chromatin remodeling pathway have been reported in pediatric GBMs. H3.3 (H3F3A) mutations may affect transcriptional regulation by altered global histone-methylation. Therefore, we analyzed yet partly understood global histone code (H3K-4/9/27/36) trimethylation pattern in H3F3A-ATRX mutants and wild-type. H3F3A, HIST1H3B, IDH1, ATRX, DAXX and Tp53 mutations were identified by sequencing/immunohistochemistry in 27 pediatric GBMs. Global histone-methylation H3K-4/9/27/36me3 and Polycomb-protein EZH2 expression were evaluated by immunohistochemistry. H3F3A-ATRX mutation was observed in 66.7 % (18/27) of pediatric GBMs. K27M and G34R-H3F3A mutations were found in 37 % (10/27) and 14.8 % (4/27) patients respectively. G34V-H3F3A, HIST1H3B and IDH1 mutations were absent. Notably, commonest global histone-methylation mark lost was H3K27me3 (17/25, 68 %) followed by H3K4me3 (45.5 %, 10/22) and H3K9me3 (18.2 %, 4/22). Global H3K36me3 showed no loss. Most significant observation was loss of one or more histone-trimethylation mark in 80 % (20/25) pediatric GBMs. Notably, simultaneous loss of H3K27me3 and H3K4me3 were present in 7/22 (31.8 %) of pediatric GBMs. Low expression of EZH2 was found in 12/24 (50 %) of cases. However no significant correlation of loss of histone-marks or EZH2 expression with H3F3A-ATRX mutants (loss of at least one histone-marks in 87.5 % (14/16) cases) versus wild-types (loss of at least one histone-marks in 75 % (6/8) cases) was seen. The present study highlights for the first time combinatorial loss of one or more histone-trimethylation marks associated with majority of pediatric GBMs and the finding suggests significant role of histone-code in the molecular biology that underlies pediatric GBMs. Hence therapies for patients with particular combinations of histone modifications present opportunity to design innovative patient-tailored treatment protocols. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| France | 1 | 33% |
| Unknown | 2 | 67% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 79 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 2 | 3% |
| Czechia | 1 | 1% |
| Unknown | 76 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 15 | 19% |
| Student > Ph. D. Student | 14 | 18% |
| Student > Master | 9 | 11% |
| Student > Doctoral Student | 8 | 10% |
| Student > Postgraduate | 6 | 8% |
| Other | 15 | 19% |
| Unknown | 12 | 15% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 22 | 28% |
| Biochemistry, Genetics and Molecular Biology | 19 | 24% |
| Agricultural and Biological Sciences | 14 | 18% |
| Neuroscience | 3 | 4% |
| Immunology and Microbiology | 2 | 3% |
| Other | 2 | 3% |
| Unknown | 17 | 22% |
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 20 December 2018.
All research outputs
#6,093,723
of 22,772,779 outputs
Outputs from Journal of Neuro-Oncology
#716
of 2,964 outputs
Outputs of similar age
#84,075
of 359,669 outputs
Outputs of similar age from Journal of Neuro-Oncology
#5
of 55 outputs
Altmetric has tracked 22,772,779 research outputs across all sources so far. This one has received more attention than most of these and is in the 73rd percentile.
So far Altmetric has tracked 2,964 research outputs from this source. They receive a mean Attention Score of 4.2. This one has done well, scoring higher than 75% of its peers.
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We're also able to compare this research output to 55 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 90% of its contemporaries.