| Title |
Methylation-based classification of benign and malignant peripheral nerve sheath tumors
|
|---|---|
| Published in |
Acta Neuropathologica, February 2016
|
| DOI | 10.1007/s00401-016-1540-6 |
| Pubmed ID | |
| Authors |
Manuel Röhrich, Christian Koelsche, Daniel Schrimpf, David Capper, Felix Sahm, Annekathrin Kratz, Jana Reuss, Volker Hovestadt, David T. W. Jones, Melanie Bewerunge-Hudler, Albert Becker, Joachim Weis, Christian Mawrin, Michel Mittelbronn, Arie Perry, Victor-Felix Mautner, Gunhild Mechtersheimer, Christian Hartmann, Ali Fuat Okuducu, Mirko Arp, Marcel Seiz-Rosenhagen, Daniel Hänggi, Stefanie Heim, Werner Paulus, Jens Schittenhelm, Rezvan Ahmadi, Christel Herold-Mende, Andreas Unterberg, Stefan M. Pfister, Andreas von Deimling, David E. Reuss |
| Abstract |
The vast majority of peripheral nerve sheath tumors derive from the Schwann cell lineage and comprise diverse histological entities ranging from benign schwannomas and neurofibromas to high-grade malignant peripheral nerve sheath tumors (MPNST), each with several variants. There is increasing evidence for methylation profiling being able to delineate biologically relevant tumor groups even within the same cellular lineage. Therefore, we used DNA methylation arrays for methylome- and chromosomal profile-based characterization of 171 peripheral nerve sheath tumors. We analyzed 28 conventional high-grade MPNST, three malignant Triton tumors, six low-grade MPNST, four epithelioid MPNST, 33 neurofibromas (15 dermal, 8 intraneural, 10 plexiform), six atypical neurofibromas, 43 schwannomas (including 5 NF2 and 5 schwannomatosis associated cases), 11 cellular schwannomas, 10 melanotic schwannomas, 7 neurofibroma/schwannoma hybrid tumors, 10 nerve sheath myxomas and 10 ganglioneuromas. Schwannomas formed different epigenomic subgroups including a vestibular schwannoma subgroup. Cellular schwannomas were not distinct from conventional schwannomas. Nerve sheath myxomas and neurofibroma/schwannoma hybrid tumors were most similar to schwannomas. Dermal, intraneural and plexiform neurofibromas as well as ganglioneuromas all showed distinct methylation profiles. Atypical neurofibromas and low-grade MPNST were indistinguishable with a common methylation profile and frequent losses of CDKN2A. Epigenomic analysis finds two groups of conventional high-grade MPNST sharing a frequent loss of neurofibromin. The larger of the two groups shows an additional loss of trimethylation of histone H3 at lysine 27 (H3K27me3). The smaller one retains H3K27me3 and is found in spinal locations. Sporadic MPNST with retained neurofibromin expression did not form an epigenetic group and most cases could be reclassified as cellular schwannomas or soft tissue sarcomas. Widespread immunohistochemical loss of H3K27me3 was exclusively seen in MPNST of the main methylation cluster, which defines it as an additional useful marker for the differentiation of cellular schwannoma and MPNST. |
X Demographics
The data shown below were collected from the profiles of 7 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Pakistan | 1 | 14% |
| Australia | 1 | 14% |
| United States | 1 | 14% |
| Unknown | 4 | 57% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 5 | 71% |
| Practitioners (doctors, other healthcare professionals) | 1 | 14% |
| Science communicators (journalists, bloggers, editors) | 1 | 14% |
Mendeley readers
The data shown below were compiled from readership statistics for 124 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 1 | <1% |
| Unknown | 123 | 99% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 20 | 16% |
| Student > Bachelor | 13 | 10% |
| Student > Ph. D. Student | 12 | 10% |
| Student > Doctoral Student | 12 | 10% |
| Other | 10 | 8% |
| Other | 26 | 21% |
| Unknown | 31 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 44 | 35% |
| Biochemistry, Genetics and Molecular Biology | 17 | 14% |
| Agricultural and Biological Sciences | 10 | 8% |
| Neuroscience | 4 | 3% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 2% |
| Other | 11 | 9% |
| Unknown | 35 | 28% |
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 27 February 2023.
All research outputs
#7,205,554
of 25,374,917 outputs
Outputs from Acta Neuropathologica
#1,416
of 2,527 outputs
Outputs of similar age
#109,619
of 407,714 outputs
Outputs of similar age from Acta Neuropathologica
#28
of 36 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. This one has received more attention than most of these and is in the 71st percentile.
So far Altmetric has tracked 2,527 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 16.8. This one is in the 43rd percentile – i.e., 43% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 407,714 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 72% of its contemporaries.
We're also able to compare this research output to 36 others from the same source and published within six weeks on either side of this one. This one is in the 25th percentile – i.e., 25% of its contemporaries scored the same or lower than it.