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Brain Pathology (Zurich, Switzerland) Jul 2009In the present study, DNA from 28 pediatric low-grade astrocytomas was analyzed using Illumina HumanHap550K single-nucleotide polymorphism oligonucleotide arrays. A...
In the present study, DNA from 28 pediatric low-grade astrocytomas was analyzed using Illumina HumanHap550K single-nucleotide polymorphism oligonucleotide arrays. A novel duplication in chromosome band 7q34 was identified in 17 of 22 juvenile pilocytic astrocytomas and three of six fibrillary astrocytomas. The 7q34 duplication spans 2.6 Mb of genomic sequence and contains approximately 20 genes, including two candidate tumor genes, HIPK2 and BRAF. There were no abnormalities in HIPK2, and analysis of two mutation hot-spots in BRAF revealed a V600E mutation in only one tumor without the duplication. Fluorescence in situ hybridization confirmed the 7q34 copy number change and was suggestive of a tandem duplication. Reverse transcription polymerase chain reaction-based sequencing revealed a fusion product between KIAA1549 and BRAF. The predicted fusion product includes the BRAF kinase domain and lacks the auto-inhibitory N-terminus. Western blot analysis revealed phosphorylated mitogen-activated protein kinase (MAPK) protein in tumors with the duplication, consistent with BRAF-induced activation of the pathway. Further studies are required to determine the role of this fusion gene in downstream MAPK signaling and its role in development of pediatric low-grade astrocytomas.
Topics: Adolescent; Adult; Astrocytoma; Blotting, Western; Brain Neoplasms; Child; Child, Preschool; Chromosomes, Human, Pair 7; DNA Mutational Analysis; Female; Humans; In Situ Hybridization, Fluorescence; Infant; MAP Kinase Signaling System; Male; Oligonucleotide Array Sequence Analysis; Oncogene Proteins, Fusion; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins B-raf; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 19016743
DOI: 10.1111/j.1750-3639.2008.00225.x -
Journal of Neuro-oncology May 2008We evaluated and compared tumor antigen precursor protein (TAPP) profiles in adult and pediatric brain tumors of 31 genes related to tumor associated antigens (TAA) for...
OBJECTIVES
We evaluated and compared tumor antigen precursor protein (TAPP) profiles in adult and pediatric brain tumors of 31 genes related to tumor associated antigens (TAA) for possible use in immunotherapy. Antigens were selected based on their potential to stimulate T cell responses against tumors of neuroectodermal origin.
METHODS
Thirty-seven brain tumor specimens from 11 adult and 26 pediatric patients were analyzed by quantitative real-time PCR for the relative expression of 31 TAPP mRNAs. The age range of adults (4F:7M) was 27-77 years (median 51.5 +/- 14.5 years) and for pediatrics (12F:14M) was 0.9-19 years (median 8.3 +/- 5.5 years). Histological diagnoses consisted of 16 glioblastomas, 4 low grade astrocytomas, 10 juvenile pilocytic astrocytomas, and 7 ependymomas.
RESULTS
The adult gliomas expressed 94% (29 of 31) of the TAPP mRNAs evaluated compared with pediatric brain tumors that expressed 55-74% of the TAPP mRNAs, dependent on tumor histological subtype. Four types of TAPP expression patterns were observed: (1) equal expression among adult and pediatric cases, (2) greater expression in adult than pediatric cases, (3) expression restricted to adult GBM and (4) a random distribution. The pediatric brain tumors lacked expression of some genes associated with engendering tumor survival, such as hTert and Survivin.
CONCLUSIONS
The potential TAA targets identified from the TAPP profiles of 31 genes associated with adult and pediatric brain tumors may help investigators select specific target antigens for developing dendritic cell- or peptide-based vaccines or T cell-based immunotherapeutic approaches against brain tumors.
Topics: Adolescent; Adult; Aged; Aging; Antigens, Neoplasm; Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; Child; Child, Preschool; Ependymoma; Female; Glioblastoma; Humans; Immunotherapy; Male; Middle Aged; Protein Precursors; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 18259692
DOI: 10.1007/s11060-008-9534-4 -
AJNR. American Journal of Neuroradiology 2006Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps provide information at MR imaging that may reflect cell attenuation and integrity. We...
BACKGROUND AND PURPOSE
Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps provide information at MR imaging that may reflect cell attenuation and integrity. We hypothesized that cerebellar tumors in children can be differentiated by their ADC values.
METHODS
Brain MR imaging studies that included ADC maps were retrospectively reviewed in 32 patients with histologically proved cerebellar neoplasm. There were 17 juvenile pilocytic astrocytomas (JPA), 8 medulloblastomas, 5 ependymomas, and 2 rhabdoid (atypical teratoid/rhabdoid tumor [AT/RT]) tumors. Absolute ADC values of contrast-enhancing solid tumor regions and ADC ratios (ADC of solid tumor to ADC of normal-appearing white matter) were compared with the histologic diagnosis. ADC values and ratios of JPAs, medulloblastomas, and ependymomas were compared by using a 2-tailed t test and one-way analysis of variance (ANOVA).
RESULTS
ADC values were significantly higher in pilocytic astrocytomas (1.65 +/- 0.27) (mean +/- SD) than in ependymomas (1.10 +/- 0.11) (P = .0003) and medulloblastomas (0.66 +/- 0.15) (P < .0001). Ependymomas demonstrated significantly higher ADC values than medulloblastomas (P = .0005). The observed differences were statistically significant on ANOVA (P < .001). ADC ratios were also significantly different among these 3 tumor types. AT/RT ADC values were similar to medulloblastoma. The range of ADC values and ratios within JPAs and ependymomas did not overlap with that of medulloblastomas.
CONCLUSION
Assessment of ADC values of enhancing solid tumor is a simple and reliable technique for preoperative differentiation of cerebellar tumors in pediatric patients. Our cutoff values of >1.4 x 10(3) mm(2)/s for JPA and <0.9 x 10(3) mm(2)/s for medulloblastoma were 100% specific.
Topics: Adolescent; Adult; Astrocytoma; Cerebellar Neoplasms; Child; Child, Preschool; Diagnosis, Differential; Diffusion Magnetic Resonance Imaging; Ependymoma; Female; Humans; Infant; Male; Medulloblastoma
PubMed: 16775298
DOI: No ID Found -
Developmental Medicine and Child... Mar 2002Although clinical syndromes of visual-spatial neglect have been well described in adults, clinical features of neglect associated with subcortical dysfunction are...
Although clinical syndromes of visual-spatial neglect have been well described in adults, clinical features of neglect associated with subcortical dysfunction are infrequently reported in children and have not been described in detail. Unilateral visual-spatial neglect in a 7-year-old male following removal of a right subcortical juvenile pilocytic astrocytoma is reported. Preoperative baseline neurocognitive assessment of the patient established intact attentional and intellectual functioning. Postoperatively visual-spatial neglect was observed that was not accounted for by the patient's visual field deficit. Consistent with classic features of attentional neglect, increases in attentional demands led to greater errors in performance. The risk of unilateral neglect following resection of subcortical tumors that abut the thalamus or disrupt thalamo-cortical projections was confirmed in a retrospective analysis of patients referred for neurocognitive testing at our site. It was concluded that the ventral thalamus may play a role in visual-spatial attention early in development.
Topics: Astrocytoma; Attention; Brain Neoplasms; Child; Functional Laterality; Hemianopsia; Humans; Intelligence Tests; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Neurosurgical Procedures; Paresis; Perceptual Disorders; Space Perception; Stereotaxic Techniques; Thalamus; Tomography, X-Ray Computed; Visual Fields
PubMed: 12008674
DOI: 10.1017/s001216220100192x -
Brain Pathology (Zurich, Switzerland) Jul 1999In adults, the TP53 tumor suppressor gene is frequently mutated in astrocytic brain tumors which is supposed to represent an early event in their development. In...
In adults, the TP53 tumor suppressor gene is frequently mutated in astrocytic brain tumors which is supposed to represent an early event in their development. In juvenile pilocytic and low-grade astrocytomas, however, TP53 mutations have until now been reported as rare, which has led to the suggestion that these tumors may follow a different molecular pathogenesis with an involvement of genes other than TP53. Our analysis of 20 pilocytic and two low-grade astrocytomas of childhood, based on a comprehensive denaturing gradient gel electrophoresis (DGGE) mutation detection assay of the entire coding region, including all splice site junctions of TP53, showed mutations considered as causative in 7 of the 20 (35%) pilocytic astrocytomas and in one of the two low-grade astrocytomas. Our finding is significantly different from the mutation frequency of 1.3% (2/155) previously reported for these tumor types. This may be attributed to the mutation detection system used, which also detects mutations occurring outside the evolutionary conserved region of TP53. Our results suggest that, contrary to the present notion, TP53 mutations may well play a role in the development of juvenile astrocytomas. Furthermore, no mutations were found in tumors of patients with progression of residual tumor after postoperative follow-up. This suggests that TP53 mutations may be associated with less aggressive forms of juvenile astrocytomas, analogous to the situation in adult astrocytomas.
Topics: Adolescent; Amino Acid Substitution; Astrocytoma; Child; Child, Preschool; DNA Mutational Analysis; Electrophoresis, Polyacrylamide Gel; Exons; Homozygote; Humans; Infant; Infant, Newborn; Introns; Mutation; Neoplasm, Residual; Polymerase Chain Reaction; Polymorphism, Genetic; Tumor Suppressor Protein p53
PubMed: 10416986
DOI: 10.1111/j.1750-3639.1999.tb00535.x -
Journal of Nuclear Medicine : Official... May 1998This study evaluates the usefulness of PET for the preoperative evaluation of brain gliomas and methods of quantification of PET results. (Comparative Study)
Comparative Study
UNLABELLED
This study evaluates the usefulness of PET for the preoperative evaluation of brain gliomas and methods of quantification of PET results.
METHODS
Fifty-four patients with brain gliomas were studied by PET with 18F-fluorodeoxyglucose (FDG) (n = 45) and/or 11C-methionine (MET) (n = 41) before any treatment. Results of visual analysis, calculation of glucose consumption and five tumor-to-normal brain ratios for both tracers were correlated with two histologic grading systems and with follow-up.
RESULTS
Visual analysis (for FDG) and tumor-to-mean cortical uptake (T/MCU) ratio proved to be the best tools for the evaluation of PET results. Methionine was proven to be better than FDG at delineating low-grade gliomas. Tumor-to-mean cortical uptake ratios for FDG and MET were clearly correlated (r = 0.78), leading to the equation T/MCU(FDG) = 0.4 x T/MCU(MET). We showed a good correlation between FDG PET and histologic grading. MET uptake could not differentiate between low-grade and anaplastic astrocytomas but was significantly increased in glioblastomas. Low-grade oligodendrogliomas exhibited high uptake of FDG and MET, probably depending more on oligodendroglial cellular differentiation than on proliferative potential. Uptake was decreased in anaplastic oligodendrogliomas, probably due to dedifferentiation. Care must be taken with peculiar histologic subgroups, i.e., juvenile pilocytic astrocytomas and oligodendrogliomas, because of a discrepancy between high PET metabolism and low proliferative potential (good prognosis). Both tracers proved useful for the prediction of survival prognosis. Methionine proved slightly superior to FDG for predicting the histologic grade and prognosis of gliomas, despite the impossibility of differentiation between Grades II and III astrocytomas with MET. This superiority of MET could be explained by patient sampling (low number of Grade III gliomas submitted to examination with both tracers). The combination of both tracers improved the overall results compared to each tracer alone.
CONCLUSION
Both tracers are useful for the prediction of the histologic grade and prognosis. The apparent superiority of MET over FDG could be due to the small number of Grade III gliomas studied with both tracers.
Topics: Brain; Brain Neoplasms; Carbon Radioisotopes; Female; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Glioma; Humans; Male; Methionine; Middle Aged; Radiopharmaceuticals; Survival Analysis; Tomography, Emission-Computed
PubMed: 9591574
DOI: No ID Found -
AJNR. American Journal of Neuroradiology Mar 1998We report the common characteristics of juvenile pilocytic astrocytomas revealed by proton MR spectroscopy. (Review)
Review
PURPOSE
We report the common characteristics of juvenile pilocytic astrocytomas revealed by proton MR spectroscopy.
METHODS
Eight children with pilocytic astrocytomas were studied with proton MR spectroscopy. The selected sampling volume was approximately 4 cm3, obtained from solid tumor. To localize the sampling volume, we used point-resolved spectroscopy (PRESS) and stimulated-echo acquisition mode (STEAM) techniques to acquire long- and short-TE spectra, respectively. Spectra from PRESS and STEAM sequences were processed using Lorentzian-to-Gaussian transformation and exponential apodization, respectively. For PRESS (2000/270) spectra, peaks of creatine, choline, N-acetylaspartate (NAA), and lactate resonances were integrated; for STEAM (2000/20) spectra, we measured the amplitude of the peaks at 3.2, 2.0, 1.3 and 0.9 ppm.
RESULTS
An elevated lactate doublet was observed in the PRESS spectra. The choline/NAA ratio was 3.40. The amplitude ratios of the lipid pattern (0.9, 1.3 and 2.0 ppm) to choline were all below one.
CONCLUSION
Despite the benign histology of the tumor, which generally lacks necrosis, a lactate signal was detected in all eight patients studied. A dominant lipid pattern was not observed.
Topics: Aspartic Acid; Astrocytoma; Brain Neoplasms; Child; Child, Preschool; Choline; Humans; Infant; Lactic Acid; Lipid Metabolism; Magnetic Resonance Spectroscopy; Protons
PubMed: 9541314
DOI: No ID Found -
AJNR. American Journal of Neuroradiology Jan 1998We compared visibility of residual juvenile cerebellar pilocytic astrocytomas (JPAs) on early postoperative and follow-up MR studies to determine whether early...
PURPOSE
We compared visibility of residual juvenile cerebellar pilocytic astrocytomas (JPAs) on early postoperative and follow-up MR studies to determine whether early postoperative MR imaging has a valid role as a baseline study.
METHODS
We reviewed the MR images of 21 consecutive children who had undergone resection of cerebellar JPA. The diagnosis of residual tumor was made on the basis of nodular enhancement that corresponded to enhancing tumor on the preoperative MR studies and/or nonenhancing nodular T2 signal that corresponded to nonenhancing tumor. Because no patient received chemotherapy or radiation therapy, abnormal T2 signal or enhancement on the early postoperative study that resolved on the follow-up study was presumed to be due to peritumoral edema and/or surgical manipulation. Nodular T2 signal and/or enhancement in the tumor bed not seen on the initial postoperative MR study but present on the subsequent MR study and unchanged on serial follow-up MR studies was presumed to represent residual tumor rather than tumor that had recurred.
RESULTS
Compared with follow-up studies, the initial postoperative MR images were true-positive for residual tumor in six patients, false-positive in five, equivocal for residual tumor in four, true-negative in five, and false-negative in one. Residual tumor did not consistently enhance, and peritumoral edema and changes resulting from surgical manipulation tended to mask or simulate residual tumor.
CONCLUSION
Early postoperative MR imaging is not accurate in differentiating residual JPA from postoperative changes, and the role of early postoperative MR imaging as a baseline study for comparison with further studies is questionable.
Topics: Adolescent; Astrocytoma; Cerebellar Neoplasms; Child; Child, Preschool; Diagnosis, Differential; False Negative Reactions; False Positive Reactions; Female; Follow-Up Studies; Humans; Infant; Magnetic Resonance Imaging; Male; Neoplasm, Residual; Postoperative Period
PubMed: 9432173
DOI: No ID Found -
The American Journal of Pathology Nov 1989The serine protease inhibitor alpha 1-antichymotrypsin (ACT) has been shown to be tightly associated with the amyloid found in plaque cores and blood vessels in the...
The serine protease inhibitor alpha 1-antichymotrypsin (ACT) has been shown to be tightly associated with the amyloid found in plaque cores and blood vessels in the brains of patients with Alzheimer's disease (AD). Although the ACT found in plaques could be derived from the high levels of ACT in serum, previous Northern analysis revealed that ACT mRNA is produced locally in AD gray matter at much higher levels than in control gray matter. To determine which brain cells express ACT mRNA, we conducted in situ hybridization with 35S-labeled cRNA probes on hippocampal sections from four AD and three control cases. To identify astrocytes unequivocally, some of the hybridized sections were immunostained for glial fibrillary acidic protein, which is astrocyte-specific. Our results showed numerous astrocytes that were intensely labeled by the probe for ACT mRNA throughout the subicular gray matter of the AD cases. In contrast, astrocytes in control gray matter were rarely labeled by the probe for ACT mRNA. Examination of plaque cores in the AD subiculum showed that some astrocytes intensely labeled by the probe for ACT mRNA were closely associated with virtually every plaque core. Our results also showed many astrocytes in both AD and control white matter that were intensely labeled by the probe for ACT mRNA, and a small fraction of the astrocytes in a juvenile cerebellar astrocytoma that we examined were found to produce high levels of ACT mRNA. In every area in which astrocytes expressing ACT mRNA were found, astrocytes producing no detectable ACT message were also present. Our findings indicate that astrocytes produce the increased ACT mRNA in AD gray matter observed by Northern analysis, but they also show that ACT mRNA expression by astrocytes is not unique to AD. The presence of astrocytes expressing ACT mRNA near, and extending processes towards, plaque cores strongly suggests that some if not all of the ACT associated with amyloid plaque cores is produced by astrocytes surrounding the cores.
Topics: Alzheimer Disease; Astrocytes; Brain; Gene Expression; Nucleic Acid Hybridization; RNA Probes; RNA, Messenger; alpha 1-Antichymotrypsin
PubMed: 2817081
DOI: No ID Found -
Journal of Korean Medical Science Jun 1989A total of 697 cases of intracranial and intraspinal tumors was obtained from the pathology file of Seoul National University Hospital and Children's Hospital during the... (Comparative Study)
Comparative Study
A total of 697 cases of intracranial and intraspinal tumors was obtained from the pathology file of Seoul National University Hospital and Children's Hospital during the period of 8 years from 1980 to 1987. These tumors were classified according to WHO classification. This study was performed to understand the recent trend of the relative frequency of the central nervous system tumors among Koreans and to compare it with the previous studies in Korea and other countries. There were 663 intracranial tumors and 34 intraspinal tumors. More common intracranial tumors were pituitary adenoma, meningioma, astrocytoma and medulloblastoma, each representing 23.4%, 20.8%, 11.8%, and 5.6%, respectively. In juvenile age group (under 15 years of age), medulloblastoma, astrocytoma, ependymoma and craniopharyngioma were more commonly encountered to be 25.6%, 21.6%, 13.6% and 12%, respectively. Both sexes were equally affected among adult group, but male preponderance was observed among juvenile group (1.49:1). Nine cases of primitive neuroectodermal tumor, a unique tumor which is not listed in WHO classification, were observed and all of them occurred before the age of 20. There were 27 metastatic tumors. Our previous study encompassing previous 17 years, 1963 to 1979, showed similar overall results except for intraspinal tumors that were more commonly encountered in previous series.
Topics: Adult; Age Factors; Brain Neoplasms; Female; Humans; Incidence; Korea; Male; Middle Aged; Neoplasm Metastasis; Sex Factors; Spinal Cord Neoplasms
PubMed: 2597364
DOI: 10.3346/jkms.1989.4.2.77