Abstract:
:Pilocytic astrocytomas (PAs) are the most common brain tumors in pediatric patients and can cause significant morbidity, including chronic neurological deficiencies. They are characterized by activating alterations in the mitogen-activated protein kinase pathway, but little else is known about their development. To map the global DNA methylation profiles of these tumors, we analyzed 62 PAs and 7 normal cerebellum samples using Illumina 450K microarrays. These data revealed two subgroups of PA that separate according to tumor location (infratentorial versus supratentorial), and identified key neural developmental genes that are differentially methylated between the two groups, including NR2E1 and EN2. Integration with transcriptome microarray data highlighted significant expression differences, which were unexpectedly associated with a strong positive correlation between methylation and expression. Differentially methylated probes were often identified within the gene body and/or regions up- or downstream of the gene, rather than at the transcription start site. We also identified a large number of differentially methylated genes between cerebellar PAs and normal cerebellum, which were again enriched for developmental genes. In addition, we found a significant association between differentially methylated genes and SUZ12 binding sites, indicating potential disruption of the polycomb repressor complex 2 (PRC2). Taken together, these data suggest that PA from different locations in the brain may arise from region-specific cells of origin, and highlight the potential disruption of key developmental regulators during tumorigenesis. These findings have implications for future basic research and clinical trials, as therapeutic targets and drug sensitivity may differ according to tumor location.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Lambert SR,Witt H,Hovestadt V,Zucknick M,Kool M,Pearson DM,Korshunov A,Ryzhova M,Ichimura K,Jabado N,Fontebasso AM,Lichter P,Pfister SM,Collins VP,Jones DTdoi
10.1007/s00401-013-1124-7subject
Has Abstractpub_date
2013-08-01 00:00:00pages
291-301issue
2eissn
0001-6322issn
1432-0533journal_volume
126pub_type
杂志文章abstract::Neurofibrillary tangles were induced in the motor neurons of the rabbit spinal cord by the intrathecal injection of colchicine, vinblastine, and vincristine. The tangles stained intensely by immunofluorescence and by the peroxidase-anti-peroxidase procedure using neurofilament antisera raised against chicken brain ant...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690460
更新日期:1980-01-01 00:00:00
abstract::The most common cause of familial frontotemporal lobar degeneration with TAR DNA-binding protein-43 pathology (FTLD-TDP) has been found to be an expansion of a hexanucleotide repeat (GGGGCC) in a noncoding region of the gene C9ORF72. Hippocampal sclerosis (HpScl) is a common finding in FTLD-TDP. Our objective was to s...
journal_title:Acta neuropathologica
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doi:10.1007/s00401-013-1161-2
更新日期:2013-10-01 00:00:00
abstract::Modern neuropathology serves a key function in the multidisciplinary management of brain tumor patients. Owing to the recent advancements in molecular neurooncology, the neuropathological assessment of brain tumors is no longer restricted to provide information on a tumor's histological type and malignancy grade, but ...
journal_title:Acta neuropathologica
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abstract::The peripheral immune system plays a critical role in aging and in the response to brain injury. Emerging data suggest inflammatory responses are exacerbated in older animals following ischemic stroke; however, our understanding of these age-related changes is poor. In this work, we demonstrate marked differences in t...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-018-1859-2
更新日期:2018-07-01 00:00:00
abstract::We report a patient who showed pathological features of both multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) at autopsy. The clinical features included severe cerebellar ataxia, autonomic failure, and rigid-akinetic parkinsonism. The clinical diagnosis was MSA. Pathological examination showed se...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010100433
更新日期:2002-01-01 00:00:00
abstract::The occurrence and topographic analysis of granulovacuolar degeneration (GVD) in the hippocampal cortex of mentally normal controls (75 cases) and patients with Alzheimer's dementia (AD; 17 cases which included Alzheimer's disease and senile dementia of Alzheimer type), multi-infarct dementia (MID; 16 cases), Pick's d...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00304627
更新日期:1992-01-01 00:00:00
abstract::Little information is available regarding the morphological changes in the mitochondria in amyotrophic lateral sclerosis (ALS). In particular, mitochondrial changes in dorsal root ganglion cells have not yet been examined. We therefore conducted an electron microscopic examination of the mitochondria in dorsal root ga...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-007-0299-1
更新日期:2007-12-01 00:00:00
abstract::The suprascapular nerve from 14 horses, which had no clinical evidence of spinatus muscle atrophy, were obtained to determine whether the nerve was sub-clinically compressed at the scapular edge. The nerves were divided into three portions, proximal and distal to the scapular edge and as it reflected around it. In nin...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00688338
更新日期:1987-01-01 00:00:00
abstract::A retrospective study of 450 consecutive AIDS autopsy cases (397 males, 53 females; mean age at death 38.4 years) in Vienna, Austria, between 1984 and 1999 compares the central nervous system (CNS) findings in three cohorts: 1984-1992 (190 cases), 1993-1995 (162 cases) and 1996-1999 (98 cases, after introduction of tr...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010000245
更新日期:2000-08-01 00:00:00
abstract::A monoclonal antibody, raised against extracts from Alzheimer brain, that recognizes a phosphorylated epitope in high molecular weight neurofilament proteins and tau proteins also immunostains Alzheimer neurofibrillary tangles, neurites in senile plaques and granulovacuolar degeneration. This result suggest that granu...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00686619
更新日期:1987-01-01 00:00:00
abstract::The brain tissue obtained from ninety-five cognitively unimpaired subjects, with ages ranging from 22 to 50 years upon death, were immunohistochemically assessed for neurodegenerative changes, i.e., hyperphosphorylated tau (HPτ) and β-amyloid (Aβ) pathology in predilection neuroanatomical areas. HPτ pathology was obse...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-011-0906-z
更新日期:2012-01-01 00:00:00
abstract::Upon brain reperfusion following ischemia, there is widespread inhibition of neuronal protein synthesis that is due to phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha), which persists in selectively vulnerable neurons (SVNs) destined to die. Other investigators have shown that expression of mutant eI...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-003-0693-2
更新日期:2003-07-01 00:00:00
abstract::A 25-year-old homosexual AIDS patient presented with progressive cognitive, motor and behavioral disturbances consistent with HIV encephalopathy. CT scans demonstrated progressive diffuse brain atrophy. Neuropathology showed predominant cortical changes including severe neuronal loss corroborated by morphometry. Only ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00294450
更新日期:1991-01-01 00:00:00
abstract::Microglia are long-living resident immune cells of the brain, which secure a stable chemical and physical microenvironment necessary for the proper functioning of the central nervous system (CNS). These highly dynamic cells continuously scan their environment for pathogens and possess the ability to react to damage-in...
journal_title:Acta neuropathologica
pub_type: 杂志文章,评审
doi:10.1007/s00401-015-1524-y
更新日期:2016-03-01 00:00:00
abstract::The expression of glial fibrillary acidic protein (GFAP), vimentin, S-100 protein (S-100), HNK-1, myelin basic protein (MBP) and fibronectin was investigated immunohistochemically in 51 ethylnitrosourea (ENU)-induced neurinomas of the rat. Additionally, 90 transplantation tumors derived from ENU-induced neurinomas and...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00310927
更新日期:1991-01-01 00:00:00
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00310926
更新日期:1991-01-01 00:00:00
abstract::Activation of the MAPK signaling pathway has been shown to be a unifying molecular feature in pilocytic astrocytoma (PA). Genetically, tandem duplications at chromosome 7q34 resulting in KIAA1549-BRAF fusion genes constitute the most common mechanism identified to date. To elucidate alternative mechanisms of aberrant ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-011-0817-z
更新日期:2011-06-01 00:00:00
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 unilate...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-020-02155-5
更新日期:2020-06-01 00:00:00
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00703319
更新日期:1977-08-16 00:00:00
abstract::Canine distemper virus (CDV) causes severe immunosuppression and neurological disease in dogs, associated with demyelination, and is a model for multiple sclerosis in man. In the early stage of the infection, demyelination is associated with viral replication in the white matter. In acute demyelinating lesions there i...
journal_title:Acta neuropathologica
pub_type: 杂志文章,评审
doi:10.1007/s00401-004-0958-4
更新日期:2005-01-01 00:00:00
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690368
更新日期:1981-01-01 00:00:00
abstract::A desmoplastic primary cerebral neuroblastoma originating in the frontal lobe of a boy who died at the age of 6 years contained dense core vesicles within the cytoplasm of neoplastic cells as evidence of neuronal differentiation. Sarcomatous transformation had occurred at the time of recurrence. At autopsy, he also ha...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00688540
更新日期:1980-01-01 00:00:00
abstract::A man of 75 years of age had had lightning pains in the legs for 8 years. Clinical examination demonstrated mild pyramidal signs and involvement of the posterior columns. A morphine pump was placed in the epidural space in the lumbar region to treat the pain. He died two weeks later from a massive pulmonary embolism. ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00695497
更新日期:1987-01-01 00:00:00
abstract::The selective toxicity of silica dust for macrophages has been used to assess the role of these cells in experimental allergic neuritis (EAN). Inbred Lewis rats were inoculated with bovine dorsal roots in Freund's complete adjuvant (day 0). In two experiments, animals received 200 mg of silica dust in 1 cm3 of saline ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00687614
更新日期:1984-01-01 00:00:00
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00304638
更新日期:1992-01-01 00:00:00
abstract::The activities of three enzymes of the hexose monophosphate pathway (HMP) were measured in frozen samples of rat cerebral cortex and ethylnitrosourea-induced tumors of the rat nervous system. Results show that in most tumors, adequate amounts of glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogena...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690440
更新日期:1978-03-15 00:00:00
abstract::Ballooned neurons are histological features of several neurodegenerative diseases of the central nervous system. We describe the immunocytochemical staining of ballooned neurons in Pick's disease, unclassified dementia, corticonigral degeneration, pigment-spheroid degeneration and Alzheimer's disease. In all of these ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00688042
更新日期:1986-01-01 00:00:00
abstract::Progressive myopathy developed in two women who consumed ipecac syrup containing emetine hydrochloride to induce vomiting as part of their anorexia nervosa. Muscle biopsy specimens were characterized by severe disruption of the sarcomeres. The ultrastructural spectrum extended from "Z-band streaming" to the formation ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00686202
更新日期:1988-01-01 00:00:00
abstract::Neuropeptides have turned out to be promising new parameters, in addition to the routinely performed histochemical diagnosis, of Hirschsprung's disease (HD). Studies of the peptidergic innervation of the affected intestinal segment of patients with HD have demonstrated a marked reduction in the density of several neur...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-002-0613-x
更新日期:2003-01-01 00:00:00
abstract::It was demonstrated that New Zealand Albino rabbits sensitized to galactocerebroside had high levels of anti-galactocerebroside antibody and of immune complexes. The rabbits was high titers of immune complexes developed demyelination in the peripheral nerves. Lesion were produced in the peripheral nerves of mice by th...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690959
更新日期:1985-01-01 00:00:00