Abstract:
:Recent studies highlight the importance of BRAF alterations resulting in mitogen activated protein kinase (MAK/ERK) pathway activation in low-grade CNS tumors. We studied 106 low-grade CNS neoplasms in a cohort of primarily pediatric patients to identify the prevalence and clinicopathologic significance of these alterations. Polymerase chain reaction testing identified KIAA1549:BRAF fusions in 51 (48%) tumors overall, including 42 (60%) pilocytic astrocytomas, 4 (17%) unclassifiable low-grade gliomas, 4 (36%) low-grade glioneuronal/neuroepithelial tumors, 0 (of 5) pleomorphic xanthoastrocytomas, 0 (of 4) diffuse astrocytomas (World Health Organization grade II), and 1 (of 3, 33%) pilomyxoid astrocytoma. KIAA1549:BRAF gene fusions confirmed by sequencing included the previously reported ones involving exons 1-16/9-18 (49%), 1-15/9-18 (35%), and 1-16/11-18 (8%) and 2 fusions with novel breakpoints: 1-15/11-18 (6%) and 1-17/10-18 (1%). DNA sequencing identified BRAF mutations in 8% of tumors. BRAF mutations were absent. KIAA1549:BRAF fusions were significantly more frequent in infratentorial (57%) and optic pathway (59%) tumors versus supratentorial (19%) tumors (p = 0.001). We did not identify significantly improved progression-free survival in tumors with fusions. In summary, KIAA1549:BRAF fusions predominate in pilocytic astrocytomas but are also present in some low-grade unclassifiable gliomas and glioneuronal tumors. The prognostic and therapeutic significance of this alteration is unclear and merits further study.
journal_name
J Neuropathol Exp Neuroljournal_title
Journal of neuropathology and experimental neurologyauthors
Lin A,Rodriguez FJ,Karajannis MA,Williams SC,Legault G,Zagzag D,Burger PC,Allen JC,Eberhart CG,Bar EEdoi
10.1097/NEN.0b013e31823f2cb0subject
Has Abstractpub_date
2012-01-01 00:00:00pages
66-72issue
1eissn
0022-3069issn
1554-6578journal_volume
71pub_type
杂志文章abstract::Glial lipopigment appears in the globus pallidus without accumulating in neurons (except for late adolescence) in multiple chronic childhood diseases. In this observational study, we compared the age-related development of glial pigmentation in children with the chronic illness (cystic fibrosis) and children dying acu...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/61.4.351
更新日期:2002-04-01 00:00:00
abstract::The relevance of cerebral amyloid angiopathy (CAA) to the pathogenesis of Alzheimer disease (AD) and dementia in general emphasizes the importance of developing novel targeting approaches for detecting and treating cerebrovascular amyloid (CVA) deposits. We developed a nanoparticle-based technology that uses a monoclo...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e318225038c
更新日期:2011-08-01 00:00:00
abstract::The light and electron microscopic features of an unique retroperitoneal ganglioneuroblastoma in a four-year-old female are described. The unprecedented concurrence of Hirano, zebra, membranous cytoplasmic (MCB), and Pick bodies in the same population of neoplastic, sympathetic ganglion cells provides further evidence...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197601000-00002
更新日期:1976-01-01 00:00:00
abstract::To determine if central nervous system (CNS) microvessel endothelial cells express class II major histocompatibility complex (MHC) molecules in early demyelinating lesions in humans, cerebral white matter (WM) biopsies from patients with acute inflammatory/demyelinating conditions, including 4 with multiple sclerosis ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199904000-00005
更新日期:1999-04-01 00:00:00
abstract::Since first described, amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) of Guam has represented an important model of age-related neurodegenerative disease. ALS/PDC is characterized neuropathologically by severe widespread involvement by neurofibrillary tangles (NFTs). Over the past 30 years there...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/62.4.381
更新日期:2003-04-01 00:00:00
abstract::In an earlier study we found that a substantial percentage of mice surviving infection with canine distemper virus (CDV) slowly developed a morbid obesity syndrome. In the present study we wished to explore the role of the virus in the development of this syndrome. The distribution of viral antigen(s) in brains of pre...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199201000-00012
更新日期:1992-01-01 00:00:00
abstract::The periaqueductal gray (PAG) plays a central role in the integration of defense responses to threatening or stressful stimuli. Little is known about the neurochemical development of the human PAG around the time of birth, when the fetus makes the transition to extrauterine life and independent defense responses are n...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199604000-00003
更新日期:1996-04-01 00:00:00
abstract::Purified myelin from the peripheral nervous system of guinea pig, frog (Rana catesbeiana), rat, rabbit, beef, and human in Freund's adjuvant were injected into the Lewis rat. Groups of rats receiving injections of myelin from different species were examined for signs of dysfunction and lesions in the PNS and CNS. Inje...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197907000-00003
更新日期:1979-07-01 00:00:00
abstract::Axonal damage is the major cause of irreversible neurologic disability in patients with multiple sclerosis. Although axonal damage correlates with antibodies against neurofilament light (NF-L) protein, a major component of the axonal cytoskeleton, the possible pathogenic role of autoimmunity to axonal antigens such as...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/nen.0b013e318040ad5c
更新日期:2007-04-01 00:00:00
abstract::Whatever the cause of myelin damage of the peripheral nervous system, the initial attack on myelin by a dysimmune process may begin either at the internodal area or in the paranodal and nodal regions. The term "nodo-paranodopathy" was first applied to some "axonal Guillain-Barré syndrome" subtypes, then extended to ca...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章,评审
doi:10.1093/jnen/nlz134
更新日期:2020-03-01 00:00:00
abstract::How to assess the substantial neuronal loss in a neurodegenerative disease such as Alzheimer disease is still being debated. Recently, stereological procedures have been proposed that claim improved accuracy and statistical power, but the results of some of these investigations have been controversial. In this study w...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199711000-00004
更新日期:1997-11-01 00:00:00
abstract::The concept of the presence of mucopolysaccharides forming an interstitial ground substance in central nervous tissues is revived. The biochemical reports of both neutral and acid mucopolysaccharides in both gray and white matter of the normal brain are reviewed. The earlier histochemical reports and the histochemical...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-198001000-00001
更新日期:1980-01-01 00:00:00
abstract::Arteriolar tortuousities, consisting of vascular coils, loops, and spirals, appear in white matter in a subset of human cerebral vessels. Computerized morphometry was used to analyze brain sections from a broad age range of subjects to determine whether tortuosity is a phenomenon of aging or is associated with leukoar...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/nen.0b013e3180537147
更新日期:2007-05-01 00:00:00
abstract::Glomeruloid bodies (GBs), tumor-associated vascular structures with a superficial resemblance to renal glomeruli, are important histopathological features of glioblastoma multiforme, but have also been described in other types of tumors and in cerebral metastases. The purpose of this study was to elucidate the pathoge...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/62.6.655
更新日期:2003-06-01 00:00:00
abstract::Lysosomal storage disorders constitute a large group of genetic diseases, many of which are characterized by mental retardation and other neurologic symptoms. The mechanisms of neural dysfunction remain poorly understood. Because neural progenitor cells (NPCs) are fundamentally important to normal brain development an...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/nen.0b013e31812571c8
更新日期:2007-08-01 00:00:00
abstract::Neutral glycolipids and gangliosides were analyzed in 149 astrocytomas (A), 46 oligodendrogliomas (O), and 21 oligoastrocytomas (OA) to determine if specific glycolipids correlate with histologic diagnosis and grade. Positivity for asialoGM1 (GA1) and negativity for paragloboside by immuno-TLC correlated with histolog...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199912000-00006
更新日期:1999-12-01 00:00:00
abstract::Neurofibrillary tangles (NFTs) represent products of insoluble tau protein in the brains of patients with Alzheimer disease (AD). The cerebrospinal fluid (CSF) tau level is a biomarker in AD diagnosis. The soluble portion of tau protein in brain parenchyma is presumably the source for CSF tau but this has not previous...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/nlw105
更新日期:2017-01-01 00:00:00
abstract::Cerebral accumulation of amyloid-beta (Abeta) is characteristic of Alzheimer disease and of amyloid precursor protein (APP) transgenic mice. Here, we assessed the efficacy of CI-1011, an inhibitor of acyl-coenzyme A:cholesterol acyltransferase, which is suitable for clinical use, in reducing amyloid pathology in both ...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0b013e3181e77ed9
更新日期:2010-08-01 00:00:00
abstract::Alpha-synuclein (alpha-syn) is an important component of neuronal and glial inclusions in brains of patients with several neurodegenerative disorders. Sporadic inclusion-body myositis (s-IBM) is the most common progressive muscle disease of older patients. Its muscle phenotype shows several similarities with Alzheimer...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/59.7.592
更新日期:2000-07-01 00:00:00
abstract::Brainstem Lewy bodies (LB) are neuronal inclusions that are closely related to Parkinson's disease (PD). The filamentous component of LB from patients with PD contains biochemically altered neurofilaments (NF). Herein we have tested the hypothesis that the oxidized products of catechols may covalently crosslink NF. Ne...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199505000-00004
更新日期:1995-05-01 00:00:00
abstract::Experimental autoimmune neuritis (EAN) is a demyelinating disease of the peripheral nervous system (PNS). This acute inflammatory disease is mediated by CD4+ T cells and bears significant similarities to the Guillain-Barré syndrome of humans. In the present study, we investigated the function of IL-18 in T cell-mediat...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/61.7.614
更新日期:2002-07-01 00:00:00
abstract::Bcl-2, a cell death suppressor protein, is expressed during brain development but is largely down-regulated in the adult central nervous system. We previously reported strong expression of bcl-2 in small, "oligodendrocyte-like" cells (OLC) found in glioneuronal hamartias. These hamartias are microscopic cell rests fou...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/59.2.113
更新日期:2000-02-01 00:00:00
abstract::The idiopathic inflammatory myopathies are diseases of unknown etiology characterized by T cell-mediated myocytotoxicity in polymyositis and complement-mediated angiopathy of muscle fibers in dermatomyositis. A variable degree of fibrosis is present in muscles in these conditions both perimysially and endomysially. We...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199705000-00003
更新日期:1997-05-01 00:00:00
abstract::Older adults with intact cognition before death and substantial Alzheimer disease (AD) lesions at autopsy have been termed "asymptomatic AD subjects" (ASYMAD). We previously reported hypertrophy of neuronal cell bodies, nuclei, and nucleoli in the CA1 of the hippocampus (CA1), anterior cingulate gyrus, posterior cingu...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/NEN.0000000000000052
更新日期:2014-04-01 00:00:00
abstract::An experimental neuropathy in rats produced by tying loosely constrictive ligatures around one sciatic nerve has recently been shown to produce pain-related behavior that follows a reproducible time course. In the present study, we assessed the degree of thermal hyperesthesia and examined the sciatic nerves by light a...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199305000-00006
更新日期:1993-05-01 00:00:00
abstract::Lymphocytic choriomeningitis virus-induced central nervous system disease is characterized by death during a seizure approximately seven days after intracerebral inoculation. This process is mediated by thymus dependent lymphocytes, sensitized against viral antigens. Various forms of immunosuppressive treatment preven...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197701000-00003
更新日期:1977-01-01 00:00:00
abstract::Because a specific group of oligodendrogliomas is susceptible to adjuvant therapy, it is important to elucidate the biological characteristics of these tumors. In situ hybridization analyses have revealed that Olig genes are expressed in oligodendroglial lineage cells and are highly expressed in oligodendrogliomas. To...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1093/jnen/62.10.1052
更新日期:2003-10-01 00:00:00
abstract::Herpes simplex virus type 1 (HSV-1) is the cause of a serious and often fatal encephalitis. Patients who survive herpes simplex encephalitis (HSE) experience behavioral abnormalities including profound cognitive dysfunctions. We have developed a rat model of acute HSE to investigate the cognitive impairments caused by...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-199305000-00008
更新日期:1993-05-01 00:00:00
abstract::Chronic experimental allergic encephalomyelitis (EAE), produced in inbred guinea pigs given a single inoculation during the juvenile period with isologous spinal cord in complete Freund's adjuvant, has been studied by light and electron microscopy. Most animals showed a delayed onset of nurologic signs from 12 to 68 w...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197505000-00001
更新日期:1975-05-01 00:00:00
abstract::Prolonged deprivation of vitamin B12 in rhesus monkeys produced changes in the central nervous system that were indistinguishable topographically and histologically from those of human subacute combined degeneration. Ultrastructural studies of early lesions of the spinal cord disclosed a degeneration of myelin charact...
journal_title:Journal of neuropathology and experimental neurology
pub_type: 杂志文章
doi:10.1097/00005072-197805000-00006
更新日期:1978-05-01 00:00:00