| Title |
Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome
|
|---|---|
| Published in |
Acta Neuropathologica, July 2017
|
| DOI | 10.1007/s00401-017-1752-4 |
| Pubmed ID | |
| Authors |
Pooja Panwalkar, Jonathan Clark, Vijay Ramaswamy, Debra Hawes, Fusheng Yang, Christopher Dunham, Stephen Yip, Juliette Hukin, Yilun Sun, Matthew J. Schipper, Lukas Chavez, Ashley Margol, Melike Pekmezci, Chan Chung, Adam Banda, Jill M. Bayliss, Sarah J. Curry, Mariarita Santi, Fausto J. Rodriguez, Matija Snuderl, Matthias A. Karajannis, Amanda M. Saratsis, Craig M. Horbinski, Anne-Sophie Carret, Beverly Wilson, Donna Johnston, Lucie Lafay-Cousin, Shayna Zelcer, David Eisenstat, Marianna Silva, Katrin Scheinemann, Nada Jabado, P. Daniel McNeely, Marcel Kool, Stefan M. Pfister, Michael D. Taylor, Cynthia Hawkins, Andrey Korshunov, Alexander R. Judkins, Sriram Venneti |
| Abstract |
Posterior fossa ependymomas (EPN_PF) in children comprise two morphologically identical, but biologically distinct tumor entities. Group-A (EPN_PFA) tumors have a poor prognosis and require intensive therapy. In contrast, group-B tumors (EPN_PFB) exhibit excellent prognosis and the current consensus opinion recommends future clinical trials to test the possibility of treatment de-escalation in these patients. Therefore, distinguishing these two tumor subtypes is critical. EPN_PFA and EPN_PFB can be distinguished based on DNA methylation signatures, but these assays are not routinely available. We have previously shown that a subset of poorly prognostic childhood EPN_PF exhibits global reduction in H3K27me3. Therefore, we set out to determine whether a simple immunohistochemical assay for H3K27me3 could be used to segregate EPN_PFA from EPN_PFB tumors. We assembled a cohort of 230 childhood ependymomas and H3K27me3 immunohistochemistry was assessed as positive or negative in a blinded manner. H3K27me3 staining results were compared with DNA methylation-based subgroup information available in 112 samples [EPN_PFA (n = 72) and EPN_PFB tumors (n = 40)]. H3K27me3 staining was globally reduced in EPN_PFA tumors and immunohistochemistry showed 99% sensitivity and 100% specificity in segregating EPN_PFA from EPN_PFB tumors. Moreover, H3K27me3 immunostaining was sufficient to delineate patients with worse prognosis in two independent, non-overlapping cohorts (n = 133 and n = 97). In conclusion, immunohistochemical evaluation of H3K27me3 global reduction is an economic, easily available and readily adaptable method for defining high-risk EPN_PFA from low-risk posterior fossa EPN_PFB tumors to inform prognosis and to enable the design of future clinical trials. |
X Demographics
The data shown below were collected from the profiles of 25 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 | 6 | 24% |
| United Kingdom | 3 | 12% |
| Germany | 2 | 8% |
| Portugal | 1 | 4% |
| China | 1 | 4% |
| Australia | 1 | 4% |
| Spain | 1 | 4% |
| Canada | 1 | 4% |
| Unknown | 9 | 36% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 15 | 60% |
| Scientists | 7 | 28% |
| Practitioners (doctors, other healthcare professionals) | 2 | 8% |
| Science communicators (journalists, bloggers, editors) | 1 | 4% |
Mendeley readers
The data shown below were compiled from readership statistics for 133 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 133 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 22 | 17% |
| Other | 20 | 15% |
| Student > Ph. D. Student | 11 | 8% |
| Student > Doctoral Student | 11 | 8% |
| Student > Master | 11 | 8% |
| Other | 29 | 22% |
| Unknown | 29 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 49 | 37% |
| Biochemistry, Genetics and Molecular Biology | 19 | 14% |
| Neuroscience | 10 | 8% |
| Agricultural and Biological Sciences | 6 | 5% |
| Psychology | 3 | 2% |
| Other | 6 | 5% |
| Unknown | 40 | 30% |
Attention Score in Context
This research output has an Altmetric Attention Score of 20. 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 March 2023.
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#1,900,372
of 25,523,622 outputs
Outputs from Acta Neuropathologica
#407
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#35,958
of 324,961 outputs
Outputs of similar age from Acta Neuropathologica
#9
of 36 outputs
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