13 results on '"Hawkins, Cynthia"'
Search Results
2. cIMPACT‐NOW update 7: advancing the molecular classification of ependymal tumors.
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Ellison, David W., Aldape, Kenneth D., Capper, David, Fouladi, Maryam, Gilbert, Mark R., Gilbertson, Richard J., Hawkins, Cynthia, Merchant, Thomas E., Pajtler, Kristian, Venneti, Sriram, and Louis, David N.
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TUMOR classification , *INFRATENTORIAL brain tumors , *TUMOR suppressor genes , *EPENDYMOMA , *GENE fusion , *INTRACRANIAL tumors - Abstract
Advances in our understanding of the biological basis and molecular characteristics of ependymal tumors since the latest iteration of the World Health Organization (WHO) classification of CNS tumors (2016) have prompted the cIMPACT‐NOW group to recommend a new classification. Separation of ependymal tumors by anatomic site is an important principle of the new classification and was prompted by methylome profiling data to indicate that molecular groups of ependymal tumors in the posterior fossa and supratentorial and spinal compartments are distinct. Common recurrent genetic or epigenetic alterations found in tumors belonging to the main molecular groups have been used to define tumor types at intracranial sites; C11orf95 and YAP1 fusion genes for supratentorial tumors and two types of posterior fossa ependymoma defined by methylation group, PFA and PFB. A recently described type of aggressive spinal ependymoma with MYCN amplification has also been included. Myxopapillary ependymoma and subependymoma have been retained as histopathologically defined tumor types, but the classification has dropped the distinction between classic and anaplastic ependymoma. While the cIMPACT‐NOW group considered that data to inform assignment of grade to molecularly defined ependymomas are insufficiently mature, it recommends assigning WHO grade 2 to myxopapillary ependymoma and allows grade 2 or grade 3 to be assigned to ependymomas not defined by molecular status. [ABSTRACT FROM AUTHOR]
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- 2020
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3. cIMPACT‐NOW update 6: new entity and diagnostic principle recommendations of the cIMPACT‐Utrecht meeting on future CNS tumor classification and grading.
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Louis, David N., Wesseling, Pieter, Aldape, Kenneth, Brat, Daniel J., Capper, David, Cree, Ian A., Eberhart, Charles, Figarella‐Branger, Dominique, Fouladi, Maryam, Fuller, Gregory N., Giannini, Caterina, Haberler, Christine, Hawkins, Cynthia, Komori, Takashi, Kros, Johan M., Ng, HK, Orr, Brent A., Park, Sung‐Hye, Paulus, Werner, and Perry, Arie
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TUMOR classification , *TUMOR grading , *MEETINGS , *WORKS councils - Abstract
cIMPACT‐NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) was established to evaluate and make practical recommendations on recent advances in the field of CNS tumor classification, particularly in light of the rapid progress in molecular insights into these neoplasms. For Round 2 of its deliberations, cIMPACT‐NOW Working Committee 3 was reconstituted and convened in Utrecht, The Netherlands, for a meeting designed to review putative new CNS tumor types in advance of any future World Health Organization meeting on CNS tumor classification. In preparatory activities for the meeting and at the actual meeting, a list of possible entities was assembled and each type and subtype debated. Working Committee 3 recommended that a substantial number of newly recognized types and subtypes should be considered for inclusion in future CNS tumor classifications. In addition, the group endorsed a number of principles—relating to classification categories, approaches to classification, nomenclature, and grading—that the group hopes will also inform the future classification of CNS neoplasms. [ABSTRACT FROM AUTHOR]
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- 2020
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4. BRAF V600E mutant oligodendroglioma‐like tumors with chromosomal instability in adolescents and young adults.
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Fukuoka, Kohei, Mamatjan, Yasin, Ryall, Scott, Komosa, Martin, Bennett, Julie, Zapotocky, Michal, Keith, Julia, Myrehaug, Sten, Hazrati, Lili‐Naz, Aldape, Kenneth, Laperriere, Norm, Bouffet, Eric, Tabori, Uri, and Hawkins, Cynthia
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TEENAGERS , *MULTIPLE tumors , *TUMORS , *TEMPORAL lobe , *GLIOMAS , *YOUNG adults , *MEIOSIS - Abstract
We performed genome‐wide methylation analysis on 136 pediatric low‐grade gliomas, identifying a unique cluster consisting of three tumors with oligodendroglioma‐like histology, BRAF p.V600E mutations and recurrent whole chromosome gains of 7 and loss of 10. Morphologically, all showed similar features, including a diffusely infiltrative glioma composed of round nuclei with perinuclear halos, a chicken‐wire pattern of branching capillaries and microcalcification. None showed astrocytic features or characteristics suggestive of high‐grade tumors including necrosis or mitotic figures. All tumors harbored multiple chromosomal copy number abnormalities (>10 chromosomes altered), but none showed 1p/19q co‐deletion or IDH1 p.R132H mutation. Hierarchical clustering and t‐stochastic neighbor embedding analyses from DNA methylation data cluster them more closely to previously described pediatric‐type low‐grade gliomas and separate from adult gliomas. These tumors exhibit distinct clinical features; they are temporal lobe lesions occurring in adolescents and young adults with a prolonged history of seizures and all are alive with no recurrence (follow‐up 3.2 to 13.2 years). We encountered another young adult case with quite similar pathological appearance and molecular status except for TERT promoter mutation. Although the series is small, these may represent a new category of IDH wild‐type low‐grade gliomas which may be confused with "molecular GBM." Further, they highlight the heterogeneity of IDH wild‐type gliomas and the relatively indolent behavior of "pediatric‐type" gliomas. [ABSTRACT FROM AUTHOR]
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- 2020
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5. cIMPACT‐NOW: a practical summary of diagnostic points from Round 1 updates.
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Louis, David N., Ellison, David W., Brat, Daniel J., Aldape, Kenneth, Capper, David, Hawkins, Cynthia, Paulus, Werner, Perry, Arie, Reifenberger, Guido, Figarella‐Branger, Dominique, Deimling, Andreas, and Wesseling, Pieter
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TUMOR classification , *ASTROCYTOMAS , *ADULT-child relationships , *GLIOMAS - Abstract
cIMPACT‐NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) was established to provide a forum to evaluate and recommend proposed changes to future CNS tumor classifications. From 2016 to 2019 (Round 1), cIMPACT published four updates. Update 1 clarified the use of the term NOS (Not Otherwise Specified) and proposed use of the additional term NEC (Not Elsewhere Classified). Update 2 issued clarifications regarding two diagnoses: Diffuse Midline Glioma, H3 K27M‐mutant and Diffuse Astrocytoma/Anaplastic Astrocytoma, IDH‐mutant. Update 3 proposed molecular criteria that could be used in the setting of an IDH‐wildtype diffuse or anaplastic astrocytic glioma without histological features of glioblastoma to infer that the tumor would behave similarly to a grade IV glioblastoma. Update 4 suggested that, in children and young adults, subtypes of IDH‐wildtype/H3‐wildtype diffuse gliomas may have distinct clinical features in the setting of a BRAFV600E mutation, FGFR1 alteration, other MAPK pathway alteration, or a MYB or MYBL1 rearrangement. The practical diagnostic relevance of these cIMPACT proposals is highlighted in this summary. [ABSTRACT FROM AUTHOR]
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- 2019
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6. Cribriform neuroepithelial tumor: molecular characterization of a SMARCB1-deficient non-rhabdoid tumor with favorable long-term outcome.
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Johann, Pascal D., Hovestadt, Volker, Thomas, Christian, Jeibmann, Astrid, Heß, Katharina, Bens, Susanne, Oyen, Florian, Hawkins, Cynthia, Pierson, Christopher R., Aldape, Kenneth, Kim, Sang‐Pyo, Widing, Eva, Sumerauer, David, Hauser, Péter, van Landeghem, Frank, Ryzhova, Marina, Korshunov, Andrey, Capper, David, Jones, David T.W., and Pfister, Stefan M.
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BRAIN tumor treatment , *METHYLATION , *DNA mutational analysis , *DIAGNOSTIC use of fluorescence in situ hybridization , *PHENOTYPES - Abstract
Rhabdoid phenotype and loss of SMARCB1 expression in a brain tumor are characteristic features of atypical teratoid/rhabdoid tumors (ATRT). Rare non-rhabdoid brain tumors showing cribriform growth pattern and SMARCB1 loss have been designated cribriform neuroepithelial tumor (CRINET). Small case series suggest that CRINETs may have a relatively favorable prognosis. However, the long-term outcome is unclear and it remains uncertain whether CRINET represents a distinct entity or a variant of ATRT. Therefore, 10 CRINETs were clinically and molecularly characterized and compared with 10 ATRTs of each of three recently described molecular subgroups (i.e. ATRT-TYR, ATRT-SHH and ATRT-MYC) using Illumina Infinium HumanMethylation450 arrays, FISH, MLPA, and sequencing. Furthermore, outcome was compared to a larger cohort of 27 children with ATRT-TYR. Median age of the 6 boys and 4 girls harboring a CRINET was 20 months. On histopathological examination, all CRINETs demonstrated a cribriform growth pattern and distinct tyrosinase staining. On unsupervised cluster analysis of methylation data, all CRINETs examined exclusively clustered within the ATRT-TYR molecular subgroup. As ATRT-TYR, CRINETs mainly showed large heterozygous 22q deletions (9/10) and SMARCB1 mutations of the other allele. In two patients, SMARCB1 mutations were also present in the germline. Estimated mean overall survival in patients with CRINETs was 125 months (95% confidence interval 100-151 months) as compared to only 53 (33-74) months in patients with ATRTs of the ATRT-TYR subgroup (Log-Rank P < 0.05). In conclusion, CRINET represents a SMARCB1-deficient non-rhabdoid tumor, which shares molecular similarities with the ATRT-TYR subgroup but has distinct histopathological features and favorable long-term outcome. [ABSTRACT FROM AUTHOR]
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- 2017
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7. International Society of Neuropathology-Haarlem Consensus Guidelines for Nervous System Tumor Classification and Grading.
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Louis, David N., Perry, Arie, Burger, Peter, Ellison, David W., Reifenberger, Guido, Deimling, Andreas von, Aldape, Kenneth, Brat, Daniel, Peter Collins, V., Eberhart, Charles, Figarella-Branger, Dominique, Fuller, Gregory N., Giangaspero, Felice, Giannini, Caterina, Hawkins, Cynthia, Kleihues, Paul, Korshunov, Andrey, Kros, Johan M., Beatriz Lopes, M., and Ho-Keung Ng
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NEUROLOGICAL disorders , *TUMOR classification , *NERVOUS system tumors , *MOLECULAR pathology - Abstract
Major discoveries in the biology of nervous system tumors have raised the question of how non-histological data such as molecular information can be incorporated into the next World Health Organization (WHO) classification of central nervous system tumors. To address this question, a meeting of neuropathologists with expertise in molecular diagnosis was held in Haarlem, the Netherlands, under the sponsorship of the International Society of Neuropathology (ISN). Prior to the meeting, participants solicited input from clinical colleagues in diverse neuro-oncological specialties. The present "white paper" catalogs the recommendations of the meeting, at which a consensus was reached that incorporation of molecular information into the next WHO classification should follow a set of provided "ISN-Haarlem" guidelines. Salient recommendations include that (i) diagnostic entities should be defined as narrowly as possible to optimize interobserver reproducibility, clinicopathological predictions and therapeutic planning; (ii) diagnoses should be "layered" with histologic classification, WHO grade and molecular information listed below an "integrated diagnosis"; (iii) determinations should be made for each tumor entity as to whether molecular information is required, suggested or not needed for its definition; (iv) some pediatric entities should be separated from their adult counterparts; (v) input for guiding decisions regarding tumor classification should be solicited from experts in complementary disciplines of neuro-oncology; and (iv) entity-specific molecular testing and reporting formats should be followed in diagnostic reports. It is hoped that these guidelines will facilitate the forthcoming update of the fourth edition of the WHO classification of central nervous system tumors. [ABSTRACT FROM AUTHOR]
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- 2014
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8. International Society of Neuropathology- Haarlem Consensus Guidelines for Nervous System Tumor Classification and Grading.
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Louis, David N., Perry, Arie, Burger, Peter, Ellison, David W., Reifenberger, Guido, Deimling, Andreas, Aldape, Kenneth, Brat, Daniel, Collins, V. Peter, Eberhart, Charles, Figarella‐Branger, Dominique, Fuller, Gregory N., Giangaspero, Felice, Giannini, Caterina, Hawkins, Cynthia, Kleihues, Paul, Korshunov, Andrey, Kros, Johan M., Beatriz Lopes, M., and Ng, Ho‐Keung
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NEUROLOGICAL disorders , *TUMORS , *PATHOLOGY , *BRAIN diseases , *HISTOLOGY , *ONCOLOGY - Abstract
Major discoveries in the biology of nervous system tumors have raised the question of how non-histological data such as molecular information can be incorporated into the next World Health Organization ( WHO) classification of central nervous system tumors. To address this question, a meeting of neuropathologists with expertise in molecular diagnosis was held in Haarlem, the Netherlands, under the sponsorship of the International Society of Neuropathology ( ISN). Prior to the meeting, participants solicited input from clinical colleagues in diverse neuro-oncological specialties. The present 'white paper' catalogs the recommendations of the meeting, at which a consensus was reached that incorporation of molecular information into the next WHO classification should follow a set of provided ' ISN- Haarlem' guidelines. Salient recommendations include that (i) diagnostic entities should be defined as narrowly as possible to optimize interobserver reproducibility, clinicopathological predictions and therapeutic planning; (ii) diagnoses should be 'layered' with histologic classification, WHO grade and molecular information listed below an 'integrated diagnosis'; (iii) determinations should be made for each tumor entity as to whether molecular information is required, suggested or not needed for its definition; (iv) some pediatric entities should be separated from their adult counterparts; (v) input for guiding decisions regarding tumor classification should be solicited from experts in complementary disciplines of neuro-oncology; and (iv) entity-specific molecular testing and reporting formats should be followed in diagnostic reports. It is hoped that these guidelines will facilitate the forthcoming update of the fourth edition of the WHO classification of central nervous system tumors. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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9. Post-chemotherapy Maturation in Supratentorial Primitive Neuroectodermal Tumors.
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Lafay‐Cousin, Lucie, Hader, Walter, Wei, Xing Chang, Nordal, Robert, Strother, Douglas, Hawkins, Cynthia, and Chan, Jennifer A.
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CANCER chemotherapy , *TUMOR treatment , *CENTRAL nervous system diseases , *MEDULLOBLASTOMA , *SUPRATENTORIAL brain tumors - Abstract
Maturation in central nervous system embryonal tumors is an uncommon phenomenon that is mainly reported in the context of specific histological subgroups of medulloblastoma. In this report we describe two cases of histological maturation in patients with supratentorial primitive neuroectodermal tumor with strikingly different outcomes. We discuss the potential impact of such findings on treatment and outcome. [ABSTRACT FROM AUTHOR]
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- 2014
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10. Aurora Kinase B Is a Potential Therapeutic Target in Pediatric Diffuse Intrinsic Pontine Glioma.
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Buczkowicz, Pawel, Zarghooni, Maryam, Bartels, Ute, Morrison, Andrew, Misuraca, Katherine L., Chan, Tiffany, Bouffet, Eric, Huang, Annie, Becher, Oren, and Hawkins, Cynthia
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AURORA kinases , *ASTROCYTOMAS , *GENE expression , *CELL lines , *CELL cycle , *POLYMERASE chain reaction - Abstract
Pediatric high-grade astrocytomas ( HGAs) account for 15-20% of all pediatric central nervous system tumors. These neoplasms predominantly involve the supratentorial hemispheres or the pons-diffuse intrinsic pontine gliomas ( DIPG). Assumptions that pediatric HGAs are biologically similar to adult HGAs have recently been challenged, and the development of effective therapeutic modalities for DIPG and supratentorial HGA hinges on a better understanding of their biological properties. Here, 20 pediatric HGAs (9 DIPGs and 11 supratentorial HGAs) were subject to gene expression profiling following approval by the research ethics board at our institution. Many of these tumors showed expression signatures composed of genes that promote G1/S and G2/M cell cycle progression. In particular, Aurora kinase B ( AURKB) was consistently and highly overexpressed in 6/9 DIPGs and 8/11 HGAs. Array data were validated using quantitative real-time PCR and immunohistochemistry, as well as cross-validation of our data set with previously published series. Inhibition of Aurora B activity in DIPG and in pediatric HGA cell lines resulted in growth arrest accompanied by morphological changes, cell cycle aberrations, nuclear fractionation and polyploidy as well as a reduction in colony formation. Our data highlight Aurora B as a potential therapeutic target in DIPG. [ABSTRACT FROM AUTHOR]
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- 2013
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11. Telomerase Inhibition as a Novel Therapy for Pediatric Ependymoma.
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Wong, Vincent C.H., Morrison, Andrew, Tabori, Uri, and Hawkins, Cynthia E.
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BRAIN tumors , *TUMORS in children , *TELOMERASE , *DNA damage , *TUMOR growth - Abstract
Ependymomas are the third most common pediatric brain tumor with an overall survival of ∼50%. Recently, we showed that telomerase [human telomerase reverse transcriptase (hTERT)] expression is a predictor of poor outcome in pediatric ependymoma. Thus, we hypothesized that ependymomas with functional telomerase may behave more aggressively and that these patients may benefit from anti-telomerase therapy. To address our hypothesis, we investigated the effect of telomerase inhibition on primary ependymoma cells harvested at the time of surgery, as no animal models or established cell lines are readily available for this tumor. The cells were characterized for glial fibrillary acidic protein (GFAP) and hTERT expression, initial telomere length and telomerase activity. They were then subjected to telomerase inhibition (MST-312, 1 µM) and tested for effects on cell viability (MTT assay), proliferation (MIB-1), apoptosis (cleaved caspase 3) and DNA damage (γH2AX). After 72 h of telomerase inhibition, primary ependymoma cells showed a significant decrease in cell number ( P < 0.001), accompanied by increased DNA damage (γH2AX expression) ( P < 0.01) and decreased proliferative index (MIB-1) ( P < 0.01). Half showed an increase in apoptosis (cleaved caspase 3). These data suggest that telomerase inhibition may be an effective adjuvant therapy in pediatric ependymoma, potentially inducing tumor growth arrest in the short term, independent of telomere shortening. [ABSTRACT FROM AUTHOR]
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- 2010
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12. Congenital Glioblastoma: A Clinicopathologic and Genetic Analysis.
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Brat, Daniel J., Shehata, Bahig M., Castellano-Sanchez, Amilcar A., Hawkins, Cynthia, Yost, Robert B., Greco, Claudia, Mazewski, Claire, Janss, Anna, Ohgaki, Hiroko, and Perry, Arie
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GLIOBLASTOMA multiforme , *GLIOMAS , *BRAIN tumors , *TUMORS in children , *GENETIC disorders , *MEDICAL genetics - Abstract
Congenital central nervous system (CNS) tumors are uncommon, accounting for 1% of all childhood brain tumors. They present clinically either at birth or within the first 3 months. Glioblastoma (GBM) only rarely occurs congenitally and has not been fully characterized. We examined clinicopathologic features and genetic alterations of six congenital GBMs. Tumors were seen by neuroimaging as large, complex cerebral hemispheric masses. All showed classic GBM histopathology, including diffuse infiltration, dense cellularity, GFAP-positivity, high mitotic activity, endothelial proliferation and pseudopalisading necrosis. Neurosurgical procedures and adjuvant therapies varied. Survivals ranged from 4 days to 7.5 years; two of the three long-term survivors received chemotherapy, whereas the three short-term survivors did not. Paraffin-embedded tissue sections were used for FISH analysis of EGFR, chromosomes 9p21 ( p16/CDKN2A) and 10q ( PTEN/DMBT1); sequencing of PTEN and TP53; and immunohistochemistry for EGFR and p53. We uncovered 10q deletions in two cases. No EGFR amplifications, 9p21 deletions, or mutations of TP53 or PTEN were noted; however, nuclear p53 immunoreactivity was strong in 5/6 cases. Tumors were either minimally immunoreactive (n = 3) or negative (n = 3) for EGFR. We conclude that congenital GBMs show highly variable survivals. They are genetically distinct from their adult counterparts and show a low frequency of known genetic alterations. Nonetheless, the strong nuclear expression of p53 in these and other pediatric GBMs could indicate that p53 dysregulation is important to tumorigenesis. [ABSTRACT FROM AUTHOR]
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- 2007
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13. cIMPACT-NOW (the consortium to inform molecular and practical approaches to CNS tumor taxonomy): a new initiative in advancing nervous system tumor classification.
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Louis, David N., Aldape, Ken, Brat, Daniel J., Capper, David, Ellison, David W., Hawkins, Cynthia, Paulus, Werner, Perry, Arie, Reifenberger, Guido, Figarella‐Branger, Dominique, Wesseling, Pieter, Batchelor, Tracy T., Gregory Cairncross, J., Pfister, Stefan M., Rutkowski, Stefan, Weller, Michael, Wick, Wolfgang, and von Deimling, Andreas
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NEUROLOGY conferences , *CENTRAL nervous system , *TUMORS , *TAXONOMY , *MOLECULAR neurobiology - Published
- 2017
- Full Text
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