Abstract:
:Medulloblastoma comprises four distinct molecular variants with distinct genetics, transcriptomes, and outcomes. Subgroup affiliation has been previously shown to remain stable at the time of recurrence, which likely reflects their distinct cells of origin. However, a therapeutically relevant question that remains unanswered is subgroup stability in the metastatic compartment. We assembled a cohort of 12-paired primary-metastatic tumors collected in the MAGIC consortium, and established their molecular subgroup affiliation by performing integrative gene expression and DNA methylation analysis. Frozen tissues were collected and profiled using Affymetrix gene expression arrays and Illumina methylation arrays. Class prediction and hierarchical clustering were performed using existing published datasets. Our molecular analysis, using consensus integrative genomic data, establishes the unequivocal maintenance of molecular subgroup affiliation in metastatic medulloblastoma. We further validated these findings by interrogating a non-overlapping cohort of 19 pairs of primary-metastatic tumors from the Burdenko Neurosurgical Institute using an orthogonal technique of immunohistochemical staining. This investigation represents the largest reported primary-metastatic paired cohort profiled to date and provides a unique opportunity to evaluate subgroup-specific molecular aberrations within the metastatic compartment. Our findings further support the hypothesis that medulloblastoma subgroups arise from distinct cells of origin, which are carried forward from ontogeny to oncology.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Wang X,Dubuc AM,Ramaswamy V,Mack S,Gendoo DM,Remke M,Wu X,Garzia L,Luu B,Cavalli F,Peacock J,López B,Skowron P,Zagzag D,Lyden D,Hoffman C,Cho YJ,Eberhart C,MacDonald T,Li XN,Van Meter T,Northcott PA,Haibe-Kaindoi
10.1007/s00401-015-1389-0subject
Has Abstractpub_date
2015-03-01 00:00:00pages
449-57issue
3eissn
0001-6322issn
1432-0533journal_volume
129pub_type
杂志文章abstract::We present here an unusual case of papillary neuroepithelial tumor of the pineal region. The patient was a 29-year-old female who presented with headaches. A computed tomography scan revealed a tumorous lesion at the pineal region and hydrocephalus. The resected tumor was composed of columnar and cuboidal cells showin...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-004-0898-z
更新日期:2004-10-01 00:00:00
abstract::The neuropathologic findings in the brain of a National Aeronautics and Space Administration (NASA) engineer, who died subsequent to nitrogen inhalation, are reported. Findings which are unusual in other forms of anoxia included relative preservation of neurons in the Sommer sector of the hippocampus and a pattern of ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00688632
更新日期:1985-01-01 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::We studied the muscle biopsy from an asymptomatic patient with high serum creatine kinase values. Subsarcolemmal and intermyofibrillar granular inclusions were seen at the light microscopy level. Ultrastructural observation showed clusters of cylindrical spirals (CS). CS are nonspecific, morphological finding, so far ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00318582
更新日期:1995-01-01 00:00:00
abstract::Accumulation of the tau protein in fibrillar intracellular aggregates is a defining feature of multiple neurodegenerative diseases collectively referred to as tauopathies. Despite intensive study of tau, there is limited information on the formation and clearance dynamics of tau inclusions. Using rAAV vectors to media...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-021-02264-9
更新日期:2021-01-26 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::Although much work has been directed recently towards unravelling the protein chemistry of neurofibrillary tangle (NFT) and senile plaque (SP) components in Alzheimer's disease, the pathogeneses of these lesions remains largely unknown and the problem of their relationship is unresolved. In particular, although paired...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00687379
更新日期:1989-01-01 00:00:00
abstract::VM mice were inoculated by intracerebral and intraperitoneal routes with brain homogenates containing the 87V strain of scrapie. The distribution and numbers of plaques were found for the parietal cortex, cingulate cortex, corpus callosum and hippocampus/dentate in coronal sections cut at the level of the thalamus and...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00688311
更新日期:1986-01-01 00:00:00
abstract::Two young zebra siblings from consecutive pregnancies suffered from neurological disease, characterized by ventral deviation of the neck and tetraparesis which progressed to tetraplegia within a few weeks. On histological examination widespread neuronal degeneration was observed in the ventral horns of the spinal cord...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00684532
更新日期:1977-01-31 00:00:00
abstract::We describe features of a patient that broadens the clinical and pathological spectrum of neurofilament inclusion disease (NFID). The patient was a 52-year-old man with a 5--6 year history of progressive, asymmetrical spastic weakness of the upper and lower extremities; L-DOPA-unresponsive parkinsonism; and SPECT evid...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-004-0974-4
更新日期:2005-04-01 00:00:00
abstract::Behaviour of biogenic amines was studied in the brains of Mongolian gerbils subjected to unilateral occlusion of the common carotid artery. Assays on the hemispheres ipsilateral to occlusion revealed in symptom-positive animals a progressive decrease in norepinephrine and dopamine, and an increase in serotonin through...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00685142
更新日期:1976-09-15 00:00:00
abstract::Considering the possibility of a paracellular route for edema resolution we studied the microvasculature of the subependymal and subcortical white matter in hydrocephalic rats. Normal adult rats were used as controls. After injection of kaolin suspension into the cisterna magna, the animals were killed at intervals of...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00695575
更新日期:1984-01-01 00:00:00
abstract::Separation of pilocytic astrocytoma from diffuse astrocytomas frequently poses problems mostly related to small sample size. Precise classification and grading are essential due to different therapeutic strategies prompted by diagnoses of pilocytic astrocytoma WHO grade I, diffuse astrocytomas WHO grade II or anaplast...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-009-0550-z
更新日期:2009-09-01 00:00:00
abstract::The Norrbottnian type of Gaucher disease is characterized by infantile or juvenile onset and variable degrees of neurological symptoms, some of which develop only after splenectomy. A full neuropathological description of this type of Gaucher disease has not been reported previously. The brains of five patients were e...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690463
更新日期:1984-01-01 00:00:00
abstract::Defects of major histocompatibility complex (MHC) class I antigen-processing machinery (APM) components have been shown to contribute to immune escape of malignant cells. We investigated the expression of APM components in astrocytomas without detectable defects in HLA class I antigen expression and correlated it with...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-007-0231-8
更新日期:2007-08-01 00:00:00
abstract::A human glioma cell line, SA146, was initiated on precoated extracellular matrix from a stereotactic biopsy of a glioblastoma. We report modulation in the expression of glial fibrillary acidic protein (GFAP) by SA146 passed in vitro before or after xenogenic transplantation into nude mice. Immunofluorescence data show...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010050722
更新日期:1997-10-01 00:00:00
abstract::Structural proteins of cultured neurofibromatosis (NF) tumor and skin cells were studied with reference to control skin fibroblasts. In polyacrylamide gel electrophoresis (PAGE)/fluorography the banding patterns of the cell lysates were markedly similar. NF tumor cells, however, produced a 60 kD band with a stronger a...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00687332
更新日期:1984-01-01 00:00:00
abstract::Prions cause scrapie and Creutzfeldt-Jakob disease (CJD); these infectious pathogens are composed largely, if not entirely, of protein molecules. No prion-specific polynucleotide has been identified. Purified preparations of scrapie prions contain high titers (greater than or equal to 10(9.5) ID50/ml), one protein (Pr...
journal_title:Acta neuropathologica
pub_type: 杂志文章,评审
doi:10.1007/BF00687261
更新日期:1987-01-01 00:00:00
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::In almost all of the earlier reported cases of Kufs' disease, the adult form of ceroid lipofuscinosis, the diagnosis was ascertained by cerebral tissue examination, while peripheral biopsy examination revealed an apparent poor diffusion of specific lipofuscinic deposits, the finger print profiles (FPs). We report the ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s004010050866
更新日期:1998-07-01 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 long-term survival of oligodendrocytes in the absence of axons in adult animals was studied following Wallerian degeneration of the optic nerves of adult rats for periods up to 22 months. In contrast to the findings in development and in young animals, large numbers of oligodendrocytes survived during this time pe...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00308922
更新日期:1990-01-01 00:00:00
abstract::Recently, 43-kDa TAR DNA-binding protein (TDP-43) was identified as a component of ubiquitinated inclusions (UIs) in sporadic amyotrophic lateral sclerosis (SALS). To clarify whether TDP-43 immunoreactivity is present in neuronal inclusions in familial ALS (FALS), we examined immunohistochemically the brains and spina...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-007-0206-9
更新日期:2007-05-01 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::Thirty-one squirrel monkey fetuses were exposed to lead acetate given to the mothers perorally during the last three-fourths or two-thirds of pregnancy. The mean maternal blood lead concentration of the group was 37 micrograms/100 ml and the individual means ranged from 22-82 micrograms/100 ml. Examination of the cent...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00687421
更新日期:1988-01-01 00:00:00
abstract::The present study used cocultures of rat dorsal root ganglia (DRG) and peritoneal macrophages to define the role of activated complement components during demyelination. The complement cascade was activated in vitro by treatment of the cultures with natural rat serum and lipopolysaccharides. Complement activation was ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00318572
更新日期:1995-01-01 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
pub_type: 杂志文章,评审
doi:10.1007/s00401-010-0736-4
更新日期:2010-11-01 00:00:00
abstract::Histochemical investigations were carried out on skeletal muscle biopsies from ten patients with chronic progressive external ophthalmoplegia with ragged-red fibers (RRF). In addition to the RRF, mild myopathic change consisting of variation in size of both type 1 and 2 fibers was seen in all patients, as well as neur...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00689593
更新日期:1988-01-01 00:00:00
abstract::Gliomas induced in the rat by transplacental administration of ethylnitrosourea (ENU) are intensely immunoreactive for vimentin and scarcely for glial fibrillary acidic protein (GFAP). Since tumoral transformation takes place during the late fetal and early postnatal period, the sequential expression of the two glial ...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00227665
更新日期:1992-01-01 00:00:00
abstract::Adult rabbits were subjected to 4.5 Gy of whole-blody or brain alone gamma-irradiation, and their hippocampus was examined with the light and electron microscope. Pycnotic cells were found at the base of the granular layer of the dentate gyrus in the so-called subgranular zone, as soon as 3 h after irradiation, and we...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690520
更新日期:1979-12-01 00:00:00