Abstract:
:Brain tumors are the most common solid tumors of childhood, and the genetic drivers and optimal therapeutic strategies for many of the different subtypes remain unknown. Here, we identify that bithalamic gliomas harbor frequent mutations in the EGFR oncogene, only rare histone H3 mutation (in contrast to their unilateral counterparts), and a distinct genome-wide DNA methylation profile compared to all other glioma subtypes studied to date. These EGFR mutations are either small in-frame insertions within exon 20 (intracellular tyrosine kinase domain) or missense mutations within exon 7 (extracellular ligand-binding domain) that occur in the absence of accompanying gene amplification. We find these EGFR mutations are oncogenic in primary astrocyte models and confer sensitivity to specific tyrosine kinase inhibitors dependent on location within the kinase domain or extracellular domain. We initiated treatment with targeted kinase inhibitors in four children whose tumors harbor EGFR mutations with encouraging results. This study identifies a promising genomically-tailored therapeutic strategy for bithalamic gliomas, a lethal and genetically distinct brain tumor of childhood.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Mondal G,Lee JC,Ravindranathan A,Villanueva-Meyer JE,Tran QT,Allen SJ,Barreto J,Gupta R,Doo P,Van Ziffle J,Onodera C,Devine P,Grenert JP,Samuel D,Li R,Metrock LK,Jin LW,Antony R,Alashari M,Cheshier S,Whipple NS,doi
10.1007/s00401-020-02155-5subject
Has Abstractpub_date
2020-06-01 00:00:00pages
1071-1088issue
6eissn
0001-6322issn
1432-0533pii
10.1007/s00401-020-02155-5journal_volume
139pub_type
杂志文章abstract::Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the aggregation of ubiquitinated proteins in affected motor neurons. Recent studies have identified several new molecular constituents of ALS-linked cellular aggregates, including FUS, TDP-43, OPTN, UBQLN2 and the translational product...
journal_title:Acta neuropathologica
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abstract::Three weeks after inoculation of 24-day-old gnotobiotic dogs with Snyder-Hill canine distemper virus, white matter samples were taken from the primary predilection sites for canine distemper virus-associated demyelination. The plasmalogenase activity in extracts was nearly 6-fold greater than control values for a dog ...
journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010050875
更新日期:1998-08-01 00:00:00
abstract::Wistar rats were given intravenous (i.v.) horseradish peroxidase (HRP) in saline in doses commonly used to study vascular permeability and the blood-brain barrier. Samples of blood were taken from conscious animals via indwelling catheters at intervals up to 6 h after the HRP injection. Plasma concentrations of adreno...
journal_title:Acta neuropathologica
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abstract::The gastrocnemius muscles of 3 groups of 10 rats, sacrified 5, 7, and 12 days respectively, following tenotomy, were submitted to different types of fixation, fixative and embedding. The occurrence of target fibres is shown not to be an artefact due to the histological procedures. Further examination demonstrates that...
journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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doi:10.1007/BF00686627
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journal_title:Acta neuropathologica
pub_type: 杂志文章
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journal_title:Acta neuropathologica
pub_type: 杂志文章
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690850
更新日期:1979-05-15 00:00:00
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journal_title:Acta neuropathologica
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更新日期:1998-07-01 00:00:00
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journal_title:Acta neuropathologica
pub_type: 杂志文章
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abstract::In order to elucidate the role of humoral antibodies in the pathogenesis of myelin lesions in experimental allergic encephalomyelitis (EAE) a combined in vivo and in vitro study was done using rabbits immunized with the purified A1 basic protein. Rabbits injected with whole white matter were used for comparison. Demye...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00699636
更新日期:1976-12-21 00:00:00
abstract::The colonic enteric nervous system was investigated in autopsy specimens from 12 patients with familial amyloidotic neuropathy (FAP) and 9 controls. The infiltration of amyloid deposits in the enteric nervous system was studied by double staining for amyloid and nerve elements. The myenteric plexus was immunostained f...
journal_title:Acta neuropathologica
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更新日期:1999-07-01 00:00:00
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journal_title:Acta neuropathologica
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更新日期:1983-01-01 00:00:00
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journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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更新日期:2004-11-01 00:00:00
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journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
pub_type: 杂志文章
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更新日期:1988-01-01 00:00:00
abstract::The intracellular localization of myoglobin(Mb) mRNA in the skeletal muscles of normal subjects and patients with Duchenne muscular dystrophy(DMD) or amyotrophic lateral sclerosis(ALS) was examined by in situ hybridization using a biotin-labeled cDNA probe. In cross sections of normal muscles, Mb mRNA signals were dem...
journal_title:Acta neuropathologica
pub_type: 杂志文章
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更新日期:1993-01-01 00:00:00
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更新日期:2002-03-01 00:00:00
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journal_title:Acta neuropathologica
pub_type: 杂志文章
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更新日期:1993-01-01 00:00:00
abstract::Using a fluorescent antibody technique, sections of the brains of patients with senile dementia or Alzheimer's disease containing senile plaques were treated with rabbit antihuman immunoglobulins labelled with FITC (fluorescein isothiocyanate, BBL). The senile plaques and the cerebral amyloid angiopathy (drusige Entar...
journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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更新日期:1998-01-01 00:00:00
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abstract::Parkinson's disease (PD) is the most common neurodegenerative movement disorder and is characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) and the gradual appearance of α-synuclein (α-syn)-containing neuronal protein aggregates. Although the exact mechanism of...
journal_title:Acta neuropathologica
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更新日期:2020-02-01 00:00:00