49 results on '"Hawkins, Cynthia"'
Search Results
2. Recurrent posterior fossa group A (PFA) ependymoma in a young child with constitutional mismatch repair deficiency (CMMRD).
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Briggs, Mayen, Das, Anirban, Firth, Helen, Levine, Adrian, Sánchez-Ramírez, Santiago, Negm, Logine, Ercan, Ayse B., Chung, Jill, Bianchi, Vanessa, Jalloh, Ibrahim, Phyu, Poe, Thorp, Nicky, Grundy, Richard G., Hawkins, Cynthia, Trotman, Jamie, Tarpey, Patrick, Tabori, Uri, Allinson, Kieren, and Murray, Matthew J.
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EPENDYMOMA ,POSTERIOR cranial fossa ,HEREDITARY nonpolyposis colorectal cancer - Published
- 2023
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3. Impact of dedicated pediatric neuro‐oncological services in a developing country: A single‐institution, Pakistani experience.
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Hamid, Syed Ahmer, Zia, Nida, Maqsood, Sidra, Rafiq, Naila, Fatima, Mushkbar, Syed, Yumna, Tabori, Uri, Bartels, Ute, Hawkins, Cynthia, Huang, Annie, Ramsawami, Vijay, Mushtaq, Naureen, and Bouffet, Eric
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- 2022
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4. Childhood head trauma and the risk of childhood brain tumours: A case‐control study in Ontario, Canada.
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Cheng, Sierra, McLaughlin, John R., Brown, M. Catherine, Al‐Sawaihey, Hamad, Rutka, James, Bouffet, Eric, Hawkins, Cynthia, Cairney, A. Elizabeth, Ranger, Adrianna, Fleming, Adam J., Johnston, Donna, Greenberg, Mark, Malkin, David, and Hung, Rayjean J.
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BRAIN tumors ,ADVERSE childhood experiences ,NECK injuries ,SKULL fractures ,CASE-control method ,PEDIATRIC oncology ,COMPUTED tomography - Abstract
Head trauma in early childhood has been hypothesized as a potential risk factor for childhood brain tumours (CBTs). However, head trauma has not been extensively studied in the context of CBTs and existing studies have yielded conflicting results. A population‐based and hospital‐based case‐control study of children 0 to 15 years with newly diagnosed CBTs from 1997 to 2003 recruited across Ontario through paediatric oncology centres was conducted. Controls were frequency‐matched with cases by age, sex and geographical region. The association was assessed based on multivariable logistic regressions, accounting for child's age, sex, ethnicity, highest level of maternal education and maternal pack‐years of smoking during the pregnancy. Analyses were conducted separately based on age of first head trauma, sex and histology. A latency period analysis was conducted. Overall, based on 280 cases and 919 controls, CBTs were not significantly associated with previous history of head trauma (OR 1.34, 95% CI 0.96, 1.86), head trauma severity, number of head injuries, or head or neck X‐rays or computed tomography (CT) examinations. Results were consistent across sexes and histological subtypes. However, head trauma within the first year of life was significantly associated with CBTs (OR 2.00, 95% CI 1.01, 3.98), but the association diminished when adjusted for X‐ray or CT occurring during the same time period (OR 1.62, 95% CI 0.75, 3.49), albeit limited sample size. Overall, no association was observed between head trauma and CBTs among all children, while head trauma occurring within first year of life may warrant further investigation in future research. What' s new? : Head trauma in early childhood has been hypothesised as a potential risk factor for childhood brain tumours (CBTs). However, existing studies have yielded conflicting results. In this case‐control study of children aged 0–15 years with newly diagnosed brain tumours in Ontario, Canada, no overall association was observed between head trauma and CBTs among the total population of 280 cases and 919 controls. There was an association between head trauma within the first year of life and CBTs, which became non‐significant after adjusting for X‐ray and CT exposures to the head and neck in the same time period. [ABSTRACT FROM AUTHOR]
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- 2022
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5. Comprehensive analysis of the ErbB receptor family in pediatric nervous system tumors and rhabdomyosarcoma.
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Varlet, Pascale, Bouffet, Eric, Casanova, Michela, Giangaspero, Felice, Antonelli, Manila, Hargrave, Darren, Ladenstein, Ruth, Pearson, Andy, Hawkins, Cynthia, König, Fatima Barbara, Rüschoff, Josef, Schmauch, Christian, Bühnemann, Claudia, Garin‐Chesa, Pilar, Schweifer, Norbert, Uttenreuther‐Fischer, Martina, Gibson, Neil, Ittrich, Carina, Krämer, Nicole, and Solca, Flavio
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- 2022
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6. A novel central nervous system embryonal tumor successfully treated with multi‐modal therapy highlights limitation of methylation‐based tumor classification.
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Lamichhane, Ritu, Roy, Paromita, Hawkins, Cynthia, Zameer, Lateef, Gehani, Anisha, Achari, Rimpa B., Ho, Ben, Huang, Annie, Tabori, Uri, Ramaswamy, Vijay, Sukumaran, Reghu K., and Das, Anirban
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- 2022
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7. cIMPACT‐NOW update 7: advancing the molecular classification of ependymal tumors.
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Ellison, David W., Aldape, Kenneth D., Capper, David, Fouladi, Maryam, Gilbert, Mark R., Gilbertson, Richard J., Hawkins, Cynthia, Merchant, Thomas E., Pajtler, Kristian, Venneti, Sriram, and Louis, David N.
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TUMOR classification ,INFRATENTORIAL brain tumors ,TUMOR suppressor genes ,EPENDYMOMA ,GENE fusion ,INTRACRANIAL tumors - Abstract
Advances in our understanding of the biological basis and molecular characteristics of ependymal tumors since the latest iteration of the World Health Organization (WHO) classification of CNS tumors (2016) have prompted the cIMPACT‐NOW group to recommend a new classification. Separation of ependymal tumors by anatomic site is an important principle of the new classification and was prompted by methylome profiling data to indicate that molecular groups of ependymal tumors in the posterior fossa and supratentorial and spinal compartments are distinct. Common recurrent genetic or epigenetic alterations found in tumors belonging to the main molecular groups have been used to define tumor types at intracranial sites; C11orf95 and YAP1 fusion genes for supratentorial tumors and two types of posterior fossa ependymoma defined by methylation group, PFA and PFB. A recently described type of aggressive spinal ependymoma with MYCN amplification has also been included. Myxopapillary ependymoma and subependymoma have been retained as histopathologically defined tumor types, but the classification has dropped the distinction between classic and anaplastic ependymoma. While the cIMPACT‐NOW group considered that data to inform assignment of grade to molecularly defined ependymomas are insufficiently mature, it recommends assigning WHO grade 2 to myxopapillary ependymoma and allows grade 2 or grade 3 to be assigned to ependymomas not defined by molecular status. [ABSTRACT FROM AUTHOR]
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- 2020
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8. cIMPACT‐NOW update 6: new entity and diagnostic principle recommendations of the cIMPACT‐Utrecht meeting on future CNS tumor classification and grading.
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Louis, David N., Wesseling, Pieter, Aldape, Kenneth, Brat, Daniel J., Capper, David, Cree, Ian A., Eberhart, Charles, Figarella‐Branger, Dominique, Fouladi, Maryam, Fuller, Gregory N., Giannini, Caterina, Haberler, Christine, Hawkins, Cynthia, Komori, Takashi, Kros, Johan M., Ng, HK, Orr, Brent A., Park, Sung‐Hye, Paulus, Werner, and Perry, Arie
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TUMOR classification ,TUMOR grading ,MEETINGS ,WORKS councils - Abstract
cIMPACT‐NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) was established to evaluate and make practical recommendations on recent advances in the field of CNS tumor classification, particularly in light of the rapid progress in molecular insights into these neoplasms. For Round 2 of its deliberations, cIMPACT‐NOW Working Committee 3 was reconstituted and convened in Utrecht, The Netherlands, for a meeting designed to review putative new CNS tumor types in advance of any future World Health Organization meeting on CNS tumor classification. In preparatory activities for the meeting and at the actual meeting, a list of possible entities was assembled and each type and subtype debated. Working Committee 3 recommended that a substantial number of newly recognized types and subtypes should be considered for inclusion in future CNS tumor classifications. In addition, the group endorsed a number of principles—relating to classification categories, approaches to classification, nomenclature, and grading—that the group hopes will also inform the future classification of CNS neoplasms. [ABSTRACT FROM AUTHOR]
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- 2020
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9. BRAF V600E mutant oligodendroglioma‐like tumors with chromosomal instability in adolescents and young adults.
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Fukuoka, Kohei, Mamatjan, Yasin, Ryall, Scott, Komosa, Martin, Bennett, Julie, Zapotocky, Michal, Keith, Julia, Myrehaug, Sten, Hazrati, Lili‐Naz, Aldape, Kenneth, Laperriere, Norm, Bouffet, Eric, Tabori, Uri, and Hawkins, Cynthia
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TEENAGERS ,MULTIPLE tumors ,TUMORS ,TEMPORAL lobe ,GLIOMAS ,YOUNG adults ,MEIOSIS - Abstract
We performed genome‐wide methylation analysis on 136 pediatric low‐grade gliomas, identifying a unique cluster consisting of three tumors with oligodendroglioma‐like histology, BRAF p.V600E mutations and recurrent whole chromosome gains of 7 and loss of 10. Morphologically, all showed similar features, including a diffusely infiltrative glioma composed of round nuclei with perinuclear halos, a chicken‐wire pattern of branching capillaries and microcalcification. None showed astrocytic features or characteristics suggestive of high‐grade tumors including necrosis or mitotic figures. All tumors harbored multiple chromosomal copy number abnormalities (>10 chromosomes altered), but none showed 1p/19q co‐deletion or IDH1 p.R132H mutation. Hierarchical clustering and t‐stochastic neighbor embedding analyses from DNA methylation data cluster them more closely to previously described pediatric‐type low‐grade gliomas and separate from adult gliomas. These tumors exhibit distinct clinical features; they are temporal lobe lesions occurring in adolescents and young adults with a prolonged history of seizures and all are alive with no recurrence (follow‐up 3.2 to 13.2 years). We encountered another young adult case with quite similar pathological appearance and molecular status except for TERT promoter mutation. Although the series is small, these may represent a new category of IDH wild‐type low‐grade gliomas which may be confused with "molecular GBM." Further, they highlight the heterogeneity of IDH wild‐type gliomas and the relatively indolent behavior of "pediatric‐type" gliomas. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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10. Re‐irradiation with concurrent BRAF and MEK inhibitor therapy.
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Bergeron Gravel, Samuel, Bouffet, Eric, Tabori, Uri, Hawkins, Cynthia, and Tsang, Derek S.
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- 2021
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11. cIMPACT‐NOW: a practical summary of diagnostic points from Round 1 updates.
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Louis, David N., Ellison, David W., Brat, Daniel J., Aldape, Kenneth, Capper, David, Hawkins, Cynthia, Paulus, Werner, Perry, Arie, Reifenberger, Guido, Figarella‐Branger, Dominique, Deimling, Andreas, and Wesseling, Pieter
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TUMOR classification ,ASTROCYTOMAS ,ADULT-child relationships ,GLIOMAS - Abstract
cIMPACT‐NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) was established to provide a forum to evaluate and recommend proposed changes to future CNS tumor classifications. From 2016 to 2019 (Round 1), cIMPACT published four updates. Update 1 clarified the use of the term NOS (Not Otherwise Specified) and proposed use of the additional term NEC (Not Elsewhere Classified). Update 2 issued clarifications regarding two diagnoses: Diffuse Midline Glioma, H3 K27M‐mutant and Diffuse Astrocytoma/Anaplastic Astrocytoma, IDH‐mutant. Update 3 proposed molecular criteria that could be used in the setting of an IDH‐wildtype diffuse or anaplastic astrocytic glioma without histological features of glioblastoma to infer that the tumor would behave similarly to a grade IV glioblastoma. Update 4 suggested that, in children and young adults, subtypes of IDH‐wildtype/H3‐wildtype diffuse gliomas may have distinct clinical features in the setting of a BRAFV600E mutation, FGFR1 alteration, other MAPK pathway alteration, or a MYB or MYBL1 rearrangement. The practical diagnostic relevance of these cIMPACT proposals is highlighted in this summary. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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12. Survival and functional outcomes of molecularly defined childhood posterior fossa ependymoma: Cure at a cost.
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Zapotocky, Michal, Beera, Kiran, Adamski, Jenny, Laperierre, Normand, Guger, Sharon, Janzen, Laura, Lassaletta, Alvaro, Figueiredo Nobre, Liana, Bartels, Ute, Tabori, Uri, Hawkins, Cynthia, Urbach, Stacey, Tsang, Derek S., Dirks, Peter B., Taylor, Michael D., Bouffet, Eric, Mabbott, Donald J., and Ramaswamy, Vijay
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RADIOTHERAPY ,EPENDYMOMA ,INTELLIGENCE levels ,PROGRESSION-free survival ,CHILDREN - Abstract
Background: Posterior fossa ependymoma (PFE) comprises 2 groups, PF group A (PFA) and PF group B (PFB), with stark differences in outcome. However, to the authors' knowledge, the long‐term outcomes of PFA ependymoma have not been described fully. The objective of the current study was to identify predictors of survival and neurocognitive outcome in a large consecutive cohort of subgrouped patients with PFE over 30 years. Methods: Demographic, survival, and neurocognitive data were collected from consecutive patients diagnosed with PFE from 1985 through 2014 at the Hospital for Sick Children in Toronto, Ontario, Canada. Subgroup was assigned using genome‐wide methylation array and/or immunoreactivity to histone H3 K27 trimethylation (H3K27me3). Results: A total of 72 PFE cases were identified, 89% of which were PFA. There were no disease recurrences noted among patients with PFB. The 10‐year progression‐free survival rate for all patients with PFA was poor at 37.1% (95% confidence interval, 25.9%‐53.1%). Analysis of consecutive 10‐year epochs revealed significant improvements in progression‐free survival and/or overall survival over time. This pertains to the increase in the rate of gross (macroscopic) total resection from 35% to 77% and the use of upfront radiotherapy increasing from 65% to 96% over the observed period and confirmed in a multivariable model. Using a mixed linear model, analysis of longitudinal neuropsychological outcomes restricted to patients with PFA who were treated with focal irradiation demonstrated significant continuous declines in the full‐scale intelligence quotient over time with upfront conformal radiotherapy, even when correcting for hydrocephalus, number of surgeries, and age at diagnosis (‐1.33 ± 0.42 points/year; P = .0042). Conclusions: Data from a molecularly informed large cohort of patients with PFE clearly indicate improved survival over time, related to more aggressive surgery and upfront radiotherapy. However, to the best of the authors' knowledge, the current study is the first, in a subgrouped cohort, to demonstrate that this approach results in reduced neurocognitive outcomes over time. In a subgroup‐specific manner, the results of the current study demonstrate that survival among patients with posterior fossa ependymoma has improved over time, and this improvement clearly is related to a change in practice with regard to pursuing aggressive surgical resections with upfront postoperative radiotherapy in all patients. This significant improvement highlights an urgent need for the implementation of early intervention and neuroprotective strategies. [ABSTRACT FROM AUTHOR]
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- 2019
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13. Reirradiation in patients with diffuse intrinsic pontine gliomas: The Canadian experience.
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Lassaletta, Alvaro, Strother, Douglas, Laperriere, Normand, Hukin, Juliette, Vanan, Magimairajan Issai, Goddard, Karen, Lafay‐Cousin, Lucie, Johnston, Donna L., Zelcer, Shayna, Zapotocky, Michal, Rajagopal, Revathi, Ramaswamy, Vijay, Hawkins, Cynthia, Tabori, Uri, Huang, Annie, Bartels, Ute, Bouffet, Eric, and Lafay-Cousin, Lucie
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- 2018
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14. Noncompaction cardiomyopathy in an infant with Walker-Warburg syndrome.
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Abdullah, Sarah, Hawkins, Cynthia, Wilson, Gregory, Yoon, Grace, Mertens, Luc, Carter, Melissa T., and Guerin, Andrea
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Walker-Warburg syndrome (WWS) is a rare autosomal recessive, congenital muscular dystrophy that is associated with brain and eye anomalies. Several genes encoding proteins involved in α-dystroglycan glycosylation have been implicated in the aetiology of WWS. We describe a patient with nonclassical features of WWS presenting with heart failure related to noncompaction cardiomyopathy resulting in death at 4 months of age. Muscle biopsy revealed absent α-dystroglycan on immunostaining and genetic testing confirmed the diagnosis with two previously described POMT2 mutations. This is the first reported case of WWS syndrome associated with noncompaction cardiomyopathy. [ABSTRACT FROM AUTHOR]
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- 2017
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15. Prognostic relevance of miR-124-3p and its target TP53INP1 in pediatric ependymoma.
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Margolin‐Miller, Yulia, Yanichkin, Natalia, Shichrur, Keren, Toledano, Helen, Ohali, Anat, Tzaridis, Theophilos, Michowitz, Shalom, Fichman‐Horn, Suzana, Feinmesser, Meora, Pfister, Stefan M., Witt, Hendrik, Tabori, Uri, Bouffet, Eric, Ramaswamy, Vijay, Hawkins, Cynthia, Taylor, Michael D., Yaniv, Isaac, and Avigad, Smadar
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- 2017
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16. Cribriform neuroepithelial tumor: molecular characterization of a SMARCB1-deficient non-rhabdoid tumor with favorable long-term outcome.
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Johann, Pascal D., Hovestadt, Volker, Thomas, Christian, Jeibmann, Astrid, Heß, Katharina, Bens, Susanne, Oyen, Florian, Hawkins, Cynthia, Pierson, Christopher R., Aldape, Kenneth, Kim, Sang‐Pyo, Widing, Eva, Sumerauer, David, Hauser, Péter, van Landeghem, Frank, Ryzhova, Marina, Korshunov, Andrey, Capper, David, Jones, David T.W., and Pfister, Stefan M.
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BRAIN tumor treatment ,METHYLATION ,DNA mutational analysis ,DIAGNOSTIC use of fluorescence in situ hybridization ,PHENOTYPES - Abstract
Rhabdoid phenotype and loss of SMARCB1 expression in a brain tumor are characteristic features of atypical teratoid/rhabdoid tumors (ATRT). Rare non-rhabdoid brain tumors showing cribriform growth pattern and SMARCB1 loss have been designated cribriform neuroepithelial tumor (CRINET). Small case series suggest that CRINETs may have a relatively favorable prognosis. However, the long-term outcome is unclear and it remains uncertain whether CRINET represents a distinct entity or a variant of ATRT. Therefore, 10 CRINETs were clinically and molecularly characterized and compared with 10 ATRTs of each of three recently described molecular subgroups (i.e. ATRT-TYR, ATRT-SHH and ATRT-MYC) using Illumina Infinium HumanMethylation450 arrays, FISH, MLPA, and sequencing. Furthermore, outcome was compared to a larger cohort of 27 children with ATRT-TYR. Median age of the 6 boys and 4 girls harboring a CRINET was 20 months. On histopathological examination, all CRINETs demonstrated a cribriform growth pattern and distinct tyrosinase staining. On unsupervised cluster analysis of methylation data, all CRINETs examined exclusively clustered within the ATRT-TYR molecular subgroup. As ATRT-TYR, CRINETs mainly showed large heterozygous 22q deletions (9/10) and SMARCB1 mutations of the other allele. In two patients, SMARCB1 mutations were also present in the germline. Estimated mean overall survival in patients with CRINETs was 125 months (95% confidence interval 100-151 months) as compared to only 53 (33-74) months in patients with ATRTs of the ATRT-TYR subgroup (Log-Rank P < 0.05). In conclusion, CRINET represents a SMARCB1-deficient non-rhabdoid tumor, which shares molecular similarities with the ATRT-TYR subgroup but has distinct histopathological features and favorable long-term outcome. [ABSTRACT FROM AUTHOR]
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- 2017
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17. Profound clinical and radiological response to BRAF inhibition in a 2-month-old diencephalic child with hypothalamic/chiasmatic glioma.
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Lassaletta, Alvaro, Guerreiro Stucklin, Ana, Ramaswamy, Vijay, Zapotocky, Michal, McKeown, Tara, Hawkins, Cynthia, Bouffet, Eric, and Tabori, Uri
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- 2016
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18. Clinical and treatment factors determining long-term outcomes for adult survivors of childhood low-grade glioma: A population-based study.
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Krishnatry, Rahul, Zhukova, Nataliya, Guerreiro Stucklin, Ana S., Pole, Jason D., Mistry, Matthew, Fried, Iris, Ramaswamy, Vijay, Bartels, Ute, Huang, Annie, Laperriere, Normand, Dirks, Peter, Nathan, Paul C., Greenberg, Mark, Malkin, David, Hawkins, Cynthia, Bandopadhayay, Pratiti, Kieran, Mark W., Manley, Peter E., Bouffet, Eric, and Tabori, Uri
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GLIOMAS ,NERVOUS system tumors ,ASTROCYTOMAS ,GLIOBLASTOMA multiforme ,MEDULLOBLASTOMA ,BRAIN tumor treatment ,GLIOMA treatment ,AGE distribution ,BRAIN tumors ,CANCER relapse ,CANCER invasiveness ,CONFIDENCE intervals ,DATABASES ,LONGITUDINAL method ,MULTIVARIATE analysis ,PROGNOSIS ,REGRESSION analysis ,SEX distribution ,SURVIVAL analysis (Biometry) ,TIME ,TUMOR classification ,ACQUISITION of data ,PROPORTIONAL hazards models ,RETROSPECTIVE studies ,KAPLAN-Meier estimator - Abstract
Background: The determinants of outcomes for adult survivors of pediatric low-grade glioma (PLGG) are largely unknown.Methods: This study collected population-based follow-up information for all PLGG patients diagnosed in Ontario, Canada from 1985 to 2012 (n = 1202) and determined factors affecting survival. The impact of upfront radiation treatment on overall survival (OS) was determined for a cohort of Ontario patients and an independent reference cohort from the Surveillance, Epidemiology, and End Results database.Results: At a median follow-up of 12.73 years (range, 0.02-33 years), only 93 deaths (7.7%) were recorded, and the 20-year OS rate was 90.1% ± 1.1%. Children with neurofibromatosis type 1 had excellent survival and no tumor-related deaths during adulthood. Adverse risk factors included pleomorphic xanthoastrocytoma (P < .001) and a thalamic location (P < .001). For patients with unresectable tumors surviving more than 5 years after the diagnosis, upfront radiotherapy was associated with an approximately 3-fold increased risk of overall late deaths (hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.6-6.6; P = .001) and an approximately 4-fold increased risk of tumor-related deaths (HR, 4.4; 95% CI, 1.3-14.6; P = .013). In a multivariate analysis, radiotherapy was the most significant factor associated with late all-cause deaths (HR, 3.0; 95% CI, 1.3-7.0; P = .012) and tumor-related deaths (HR, 4.4; 95% CI, 1.3-14.6; P = 0.014). A similar association between radiotherapy and late deaths was observed in the independent reference cohort (P < .001). In contrast to early deaths, late mortality was associated not with PLGG progression but rather with tumor transformation and non-oncological causes.Conclusions: The course of PLGG is associated with excellent long-term survival, but this is hampered by increased delayed mortality in patients receiving upfront radiotherapy. These observations should be considered when treatment options are being weighed for these patients. [ABSTRACT FROM AUTHOR]- Published
- 2016
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19. High frequency of mismatch repair deficiency among pediatric high grade gliomas in Jordan.
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Amayiri, Nisreen, Tabori, Uri, Campbell, Brittany, Bakry, Doua, Aronson, Melyssa, Durno, Carol, Rakopoulos, Patricia, Malkin, David, Qaddoumi, Ibrahim, Musharbash, Awni, Swaidan, Maisa, Bouffet, Eric, Hawkins, Cynthia, and Al‐Hussaini, Maysa
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Biallelic mismatch repair deficiency (bMMRD) is a cancer predisposition syndrome affecting primarily individuals from consanguinous families resulting in multiple childhood cancers including high grade gliomas (HGG). This is the first study to assess the prevalence of bMMRD among patients with HGG in countries where consanguinity is high. We collected molecular and clinical information on all children diagnosed with HGG and supratentorial primitive neuroectodermal tumors (sPNET) between 2003 and 2013 at King Hussein Cancer Center, Jordan. Comparison was made to a similar cohort from Toronto. Clinical data regarding presence of café au lait macules(CAL), family history of cancer, consanguinity, pathology and treatment were collected. Tumors were centrally reviewed and tested for MMRD by immunohistochemistry of the corresponding proteins. Forty-two patients fulfilled the inclusion criteria, including 36 with HGG. MMRD was observed in 39% of HGG of whom79% also lost MMR staining in the corresponding normal cells suggestive of bMMRD. P53 dysfunction was highly enriched in MMR deficient tumors (p=0.0003). The frequency of MMRD was significantly lower in Toronto cohort (23%, p=0.03). Both evidence of CAL and consanguinity correlated with bMMRD (p=0.005 and 0.05,respectively) but family history of cancer didn't. HGG with all three bMMRD risk factors had evidence of MMRD and all children affected by multiple bMMRD related cancers had identical gene loss by immunohistochemical staining. In Jordan, the frequency of clinical and immunohistochemical alterations suggestive of bMMRD in pediatric HGG is high. Genetic testing will enable appropriate counseling and cancer screening to improve survival of these patients. [ABSTRACT FROM AUTHOR]
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- 2016
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20. RNAseq analysis for the diagnosis of muscular dystrophy.
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Gonorazky, Hernan, Liang, Minggao, Cummings, Beryl, Lek, Monkol, Micallef, Johann, Hawkins, Cynthia, Basran, Raveen, Cohn, Ronald, Wilson, Michael D., MacArthur, Daniel, Marshall, Christian R., Ray, Peter N., and Dowling, James J.
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RNA sequencing ,MUSCULAR dystrophy diagnosis ,NEUROLOGICAL disorders -- Genetic aspects ,GENETIC mutation ,GENETIC transcription - Abstract
The precise genetic cause remains elusive in nearly 50% of patients with presumed neurogenetic disease, representing a significant barrier for clinical care. This is despite significant advances in clinical genetic diagnostics, including the application of whole-exome sequencing and next-generation sequencing-based gene panels. In this study, we identify a deep intronic mutation in the DMD gene in a patient with muscular dystrophy using both conventional and RNAseq-based transcriptome analyses. The implications of our data are that noncoding mutations likely comprise an important source of unresolved genetic disease and that RNAseq is a powerful platform for detecting such mutations. [ABSTRACT FROM AUTHOR]
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- 2016
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21. EZH2 expression is a prognostic factor in childhood intracranial ependymoma: A Canadian Pediatric Brain Tumor Consortium study.
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Li, Amanda M., Dunham, Christopher, Tabori, Uri, Carret, Anne‐Sophie, McNeely, P. Daniel, Johnston, Donna, Lafay‐Cousin, Lucie, Wilson, Beverly, Eisenstat, David D., Jabado, Nada, Zelcer, Shayna, Silva, Mariana, Scheinemann, Katrin, Fryer, Christopher, Hendson, Glenda, Fotovati, Abbas, Hawkins, Cynthia, Yip, Stephen, Dunn, Sandra E., and Hukin, Juliette
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EPENDYMOMA ,PROTEIN kinase B ,GENE expression ,BIOMARKERS ,LEUKEMIA - Abstract
BACKGROUND The cure rate for childhood intracranial ependymoma is approximately 70% in the setting of a gross total resection followed by radiation, but management remains challenging in patients with residual disease. Therefore, robust biomarkers are needed to guide the development of new targeted therapy. The authors evaluated the expression of several biomarkers in pediatric intracranial ependymoma and observed that the expression of enhancer of zeste homolog 2 (EZH2), a polycomb complex protein involved in epigenetic regulation of gene expression, was independently associated with poor survival. METHODS Tissue microarray immunostaining was performed on 180 ependymoma samples from 12 of 16 Canadian pediatric centers. Expression levels of EZH2, Ki-67, B lymphoma Moloney-murine leukemia virus insertion region 1 homolog, tumor protein 16 (P16), Y-box binding protein 1, phosphorylated protein kinase B (pAKT), and epidermal growth factor receptor were evaluated. Cox regression analyses were performed, and the Kaplan-Meier method was used to construct survival curves. RESULTS EZH2 expressed in 16% of tumors was associated with inferior 5-year overall survival. Ki-67 and pAKT levels were associated with a poor outcome in patients with posterior fossa ependymoma, and the absence of P16 was associated with a poor outcome in patients with supratentorial ependymoma. Multivariate analysis revealed that younger age and EZH2 expression (95% confidence interval, 1.1-36.0) were independent markers of a poor prognosis. CONCLUSIONS EZH2 is a novel, independent marker of a poor prognosis in patients with ependymoma, especially in those who have tumors located in the posterior fossa. EZH2, pAKT, and P16 are potential therapeutic targets, particularly for patients who have tumors in which standard gross total resection plus fractionated radiotherapy is not feasible. Cancer 2015;121:1499-1507. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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22. Clinical, EEG, MRI, MEG, and surgical outcomes of pediatric epilepsy with astrocytic inclusions versus focal cortical dysplasia.
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Alshafai, Laila, Ochi, Ayako, Go, Cristina, McCoy, Blathnaid, Hawkins, Cynthia, Otsubo, Hiroshi, Snead, Orlando C., Rutka, James, and Widjaja, Elysa
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DYSPLASIA ,ASTROCYTOMAS ,CHILDHOOD epilepsy ,ELECTROENCEPHALOGRAPHY ,MAGNETOENCEPHALOGRAPHY ,MAGNETIC resonance imaging ,SPASMS - Abstract
Objective Astrocytic inclusions ( AIs) have been identified on histologic specimens of patients with early onset seizures, and the proteomic contents have been described. The aim of this study was to compare the clinical, electroencephalography ( EEG), magnetoencephalography ( MEG), magnetic resonance imaging ( MRI), and surgical outcomes of AIs relative to focal cortical dysplasia ( FCD). Methods We assessed the clinical manifestations, semiology, ictal and interictal features on video- EEG, MEG, MRI features, and surgical outcomes of children with histologically proven AIs compared to FCD. Results Six children had AIs and 27 had FCD. Children with AIs had an earlier age at seizure onset, periodic spasms (all children), and interictal epileptiform discharges consisting of a mixture of generalized or diffuse hemispheric slow waves, sharp waves, spikes and polyspikes. Children with FCD were less likely to have spasms (4/27 [15%]), and the morphology of the diffuse hemispheric or generalized discharges were different from those of AI, consisting of spike-and-waves, polyspike-and-waves, sharp-and-slow waves, and paroxysmal fast activity. Patients with AIs were less likely to have tightly clustered MEG spike sources (3/6 [50%] vs. 23/27 [85%]), and more likely to demonstrate abnormal sulcation and gyration pattern (4/6 [67%] vs. 2/27 [7%]) and gray matter heterotopia (2/6 [33%] vs. 0/27 [0%]) than patients with FCD. Four children with AIs had resection and two had biopsy but did not undergo resection. Children with AIs had lower rates of seizure freedom after surgery compared to FCD (1/4 [25%] vs. 15/27 [56%], respectively). Significance Although there were some similarities between AIs and FCD, patients with AIs were more likely to present with early onset periodic spasms, have unusual interictal epileptiform discharges, abnormal sulcation, gyration pattern, and gray matter heterotopia, and were less likely to be seizure free following surgical resection relative to FCD. Further study with a larger sample size is needed to validate our findings. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
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23. International Society of Neuropathology-Haarlem Consensus Guidelines for Nervous System Tumor Classification and Grading.
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Louis, David N., Perry, Arie, Burger, Peter, Ellison, David W., Reifenberger, Guido, Deimling, Andreas von, Aldape, Kenneth, Brat, Daniel, Peter Collins, V., Eberhart, Charles, Figarella-Branger, Dominique, Fuller, Gregory N., Giangaspero, Felice, Giannini, Caterina, Hawkins, Cynthia, Kleihues, Paul, Korshunov, Andrey, Kros, Johan M., Beatriz Lopes, M., and Ho-Keung Ng
- Subjects
NEUROLOGICAL disorders ,TUMOR classification ,NERVOUS system tumors ,MOLECULAR pathology - Abstract
Major discoveries in the biology of nervous system tumors have raised the question of how non-histological data such as molecular information can be incorporated into the next World Health Organization (WHO) classification of central nervous system tumors. To address this question, a meeting of neuropathologists with expertise in molecular diagnosis was held in Haarlem, the Netherlands, under the sponsorship of the International Society of Neuropathology (ISN). Prior to the meeting, participants solicited input from clinical colleagues in diverse neuro-oncological specialties. The present "white paper" catalogs the recommendations of the meeting, at which a consensus was reached that incorporation of molecular information into the next WHO classification should follow a set of provided "ISN-Haarlem" guidelines. Salient recommendations include that (i) diagnostic entities should be defined as narrowly as possible to optimize interobserver reproducibility, clinicopathological predictions and therapeutic planning; (ii) diagnoses should be "layered" with histologic classification, WHO grade and molecular information listed below an "integrated diagnosis"; (iii) determinations should be made for each tumor entity as to whether molecular information is required, suggested or not needed for its definition; (iv) some pediatric entities should be separated from their adult counterparts; (v) input for guiding decisions regarding tumor classification should be solicited from experts in complementary disciplines of neuro-oncology; and (iv) entity-specific molecular testing and reporting formats should be followed in diagnostic reports. It is hoped that these guidelines will facilitate the forthcoming update of the fourth edition of the WHO classification of central nervous system tumors. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
24. Duration of the pre-diagnostic interval in medulloblastoma is subgroup dependent.
- Author
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Ramaswamy, Vijay, Remke, Marc, Shih, David, Wang, Xin, Northcott, Paul A., Faria, Claudia C., Raybaud, Charles, Tabori, Uri, Hawkins, Cynthia, Rutka, James, Taylor, Michael D., and Bouffet, Eric
- Published
- 2014
- Full Text
- View/download PDF
25. Post-chemotherapy Maturation in Supratentorial Primitive Neuroectodermal Tumors.
- Author
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Lafay‐Cousin, Lucie, Hader, Walter, Wei, Xing Chang, Nordal, Robert, Strother, Douglas, Hawkins, Cynthia, and Chan, Jennifer A.
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CANCER chemotherapy ,TUMOR treatment ,CENTRAL nervous system diseases ,MEDULLOBLASTOMA ,SUPRATENTORIAL brain tumors - Abstract
Maturation in central nervous system embryonal tumors is an uncommon phenomenon that is mainly reported in the context of specific histological subgroups of medulloblastoma. In this report we describe two cases of histological maturation in patients with supratentorial primitive neuroectodermal tumor with strikingly different outcomes. We discuss the potential impact of such findings on treatment and outcome. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
26. Overcoming resistance to sonic hedgehog inhibition by targeting p90 ribosomal S6 kinase in pediatric medulloblastoma.
- Author
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Pambid, Mary Rose, Berns, Rachel, Adomat, Hans H., Hu, Kaiji, Triscott, Joanna, Maurer, Norbert, Zisman, Natalia, Ramaswamy, Vijay, Hawkins, Cynthia E., Taylor, Michael D., Dunham, Christopher, Guns, Emma, and Dunn, Sandra E.
- Published
- 2014
- Full Text
- View/download PDF
27. Loss of p53 cooperates with K-ras activation to induce glioma formation in a region-independent manner.
- Author
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Muñoz, Diana Marcela, Tung, Takyee, Agnihotri, Sameer, Singh, Sanjay, Guha, Abhijit, Zadeh, Gelareh, and Hawkins, Cynthia
- Published
- 2013
- Full Text
- View/download PDF
28. Salvage chemotherapy after failure of targeted therapy in a child with BRAF V600E low‐grade glioma.
- Author
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Raswoli, Musthafa, Nobre, Liana, Hawkins, Cynthia, Bartels, Ute Katharina, Tabori, Uri, and Bouffet, Eric
- Published
- 2021
- Full Text
- View/download PDF
29. Aurora Kinase B Is a Potential Therapeutic Target in Pediatric Diffuse Intrinsic Pontine Glioma.
- Author
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Buczkowicz, Pawel, Zarghooni, Maryam, Bartels, Ute, Morrison, Andrew, Misuraca, Katherine L., Chan, Tiffany, Bouffet, Eric, Huang, Annie, Becher, Oren, and Hawkins, Cynthia
- Subjects
AURORA kinases ,ASTROCYTOMAS ,GENE expression ,CELL lines ,CELL cycle ,POLYMERASE chain reaction - Abstract
Pediatric high-grade astrocytomas ( HGAs) account for 15-20% of all pediatric central nervous system tumors. These neoplasms predominantly involve the supratentorial hemispheres or the pons-diffuse intrinsic pontine gliomas ( DIPG). Assumptions that pediatric HGAs are biologically similar to adult HGAs have recently been challenged, and the development of effective therapeutic modalities for DIPG and supratentorial HGA hinges on a better understanding of their biological properties. Here, 20 pediatric HGAs (9 DIPGs and 11 supratentorial HGAs) were subject to gene expression profiling following approval by the research ethics board at our institution. Many of these tumors showed expression signatures composed of genes that promote G1/S and G2/M cell cycle progression. In particular, Aurora kinase B ( AURKB) was consistently and highly overexpressed in 6/9 DIPGs and 8/11 HGAs. Array data were validated using quantitative real-time PCR and immunohistochemistry, as well as cross-validation of our data set with previously published series. Inhibition of Aurora B activity in DIPG and in pediatric HGA cell lines resulted in growth arrest accompanied by morphological changes, cell cycle aberrations, nuclear fractionation and polyploidy as well as a reduction in colony formation. Our data highlight Aurora B as a potential therapeutic target in DIPG. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
30. Association between radiographic Wallerian degeneration and neuropathological changes post childhood stroke.
- Author
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JONES, KEVIN C, HAWKINS, CYNTHIA, ARMSTRONG, DEREK, DEVEBER, GABRIELLE, MACGREGOR, DAUNE, MOHARIR, MAHENDRANATH, and ASKALAN, RAND
- Subjects
- *
NEURODEGENERATION , *PYRAMIDAL tract , *DIAGNOSTIC imaging , *MAGNETIC resonance imaging , *HISTOPATHOLOGY , *AUTOPSY , *HEMORRHAGIC diseases - Abstract
Aim Wallerian degeneration is a radiological finding thought to reflect corticospinal tract degeneration. This finding on magnetic resonance imaging (MRI) is routinely used as a predictor of poor prognosis in childhood stroke. However, its validity has never been established. Our objective was to correlate Wallerian degeneration seen on MRI with histopathology. Method We searched the databases of the Department of Pathology and Children's Stroke registry at the Hospital for Sick Children, Toronto for autopsy specimens exhibiting focal infarcts from children born at term who underwent MRI after a stroke. The specimens were examined for Wallerian degeneration and then correlated with the pre-mortem MRI findings. Results Seven children (four females, three males) with a median age of 11 years (1-17y) at the time of stroke met the inclusion criteria for this study. Of the seven children included in the study with ischaemic or haemorrhagic infarcts, six had concordant Wallerian degeneration findings on both MRI and post-mortem histopathological examination. The median time between stroke and death was 20 days (3-1825d). Interpretation Our results show for the first time that the radiographic finding of Wallerian degeneration is a valid biomarker of corticospinal tract degeneration in children who have had ischaemic or haemorrhagic stroke. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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- View/download PDF
31. Overgrowth with increased proliferation of fibroblast and matrix metalloproteinase activity related to reduced TIMP1: A newly recognized syndrome?
- Author
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Chung, Brian, Hinek, Aleksander, Keating, Sarah, Weksberg, Rosanna, Shah, Vibhuti, Blaser, Susan, Hawkins, Cynthia, and Chitayat, David
- Abstract
We report on a child with prenatal onset of overgrowth associated with thick, excessive wrinkled skin and other abnormalities including cleft palate, Chiari malformation and polymicrogyria. His clinical features do not resemble any of the known reported overgrowth syndromes. Genetic evaluations, including karyotype, oligoarray, methylation-sensitive multiplex ligation-dependent probe amplification (MLPA) for 11p11.2 region, CDKN1C sequencing, GPC3 sequencing and dosage analysis, and HRAS sequencing, have been un-revealing. Immunohistochemistry done on the patient's cultured skin fibroblasts showed normally assembled elastic fibers and normal pattern of chondroitin sulfate deposition with defective deposition of Collagen I fibers. In addition, there were high levels of immuno-detectable metalloproteinase 3 (MMP3) and undetectable tissue inhibitor of metalloproteinase 1 (TIMP1). The defective collagen deposition in the fibroblast culture could be reversed by the broad spectrum MMP inhibitor, doxycycline. We also present evidence that the fibroblasts of this patient have an increased rate of cellular proliferation. We propose that this is a previously unrecognized overgrowth syndrome associated with increased cellular proliferation and defective collagen I deposition due to an imbalance between MMP and TIMP in fibroblasts. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
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32. Milder phenotype of congenital muscular dystrophy in a novel POMT1 mutation.
- Author
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Al-Zaidy, Samiah A., Baskin, Berivan, Hawkins, Cynthia, Yoon, Grace, Ray, Peter N., and Vajsar, Jiri
- Abstract
Introduction: Congenital muscular dystrophies (CMD) with hypoglycosylated α-dystroglycan due to POMT1 mutations are associated with clinical phenotypes that vary in severity. Methods: We describe a patient with congenital hypotonia, generalized weakness, elevated creatine kinase (CK), and normal brain imaging. Results: Histochemical analysis of the index case's muscle showed deficiency of glycosylated α-dystroglycan and secondary merosin deficiency. Genetic testing revealed a novel mutation in exon 20 of the POMT1 gene. Conclusions: Our patient's milder form of CMD adds to the emerging evidence of an expanding phenotype caused by POMT1 mutations. The histopathological findings of the muscle biopsy in this case support the need for careful clinical, genetic, and histochemical diagnostic interpretation. Muscle Nerve 45: 752-755, 2012 [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
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33. Favorable outcome with conservative treatment for children with low grade brainstem tumors.
- Author
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Fried, Iris, Hawkins, Cynthia, Scheinemann, Katrin, Tsangaris, Elena, Hesselson, Leila, Bartels, Ute, Huang, Annie, Laperriere, Normand, Dirks, Peter, Bouffet, Eric, and Tabori, Uri
- Published
- 2012
- Full Text
- View/download PDF
34. Supratentorial ependymoma in children: To observe or to treat following gross total resection?
- Author
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Venkatramani, Rajkumar, Dhall, Girish, Patel, Moneil, Grimm, John, Hawkins, Cynthia, McComb, Gordon, Krieger, Mark, Wong, Kenneth, O'Neil, Sharon, and Finlay, Jonathan L.
- Published
- 2012
- Full Text
- View/download PDF
35. A proteomic analysis of pediatric seizure cases associated with astrocytic inclusions.
- Author
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Visanji, Naomi P., Wong, Janice C., Wang, Simon X., Cappel, Blair, Kleinschmidt-DeMasters, Bette K., Handler, Michael H., Ochi, Ayako, Otsubo, Hiroshi, Rutka, James T., Go, Cristina, Weiss, Shelly, Vinters, Harry V., Hawkins, Cynthia E., DeSouza, Leroi V., Siu, K.W. Michael, and Hazrati, Lili-Naz
- Subjects
INFANTILE spasms ,ASTROCYTOMAS ,PROTEOMICS ,PROTEINS ,CATALASE ,CARBONIC anhydrase ,ASTROCYTES - Abstract
Summary Cerebral hyaline astrocytic inclusions have been observed in a subset of patients with early onset epilepsy, brain structural anomalies, and developmental delay, which indicates that it may represent a unique clinicopathologic entity. To further characterize this condition we use proteomics to investigate differentially expressed proteins in epileptic brain tissue from three pediatric epileptic patients with cerebral hyaline astrocytic inclusions, ranging in age from 5-13 years, and compare to brain tissue from two normal controls. Catalase and carbonic anhydrase I both exhibited increased expression in epileptic brain tissue compared to controls. These findings were confirmed by Western blot analysis. Furthermore, both proteins were localized to astrocytes and in epileptic brain were located within the cerebral hyaline astrocytic inclusions, suggesting a potential role in the generation of this pathologic feature of early onset epilepsy with cerebral hyaline astrocytic inclusions. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
36. Feasibility and efficacy of repeated chemotherapy for progressive pediatric low-grade gliomas.
- Author
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Scheinemann, Katrin, Bartels, Ute, Tsangaris, Elena, Hawkins, Cynthia, Huang, Annie, Dirks, Peter, Fried, Iris, Bouffet, Eric, and Tabori, Uri
- Published
- 2011
- Full Text
- View/download PDF
37. Brain biopsy in children with primary small-vessel central nervous system vasculitis.
- Author
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Elbers, Jorina, Halliday, William, Hawkins, Cynthia, Hutchinson, Clare, and Benseler, Susanne M.
- Abstract
Objective:: Primary angiitis of the central nervous system in childhood (cPACNS) is an immune-mediated inflammatory process directed toward blood vessels in the central nervous system. It has been associated with variable clinical and radiological presentations, and devastating consequences without treatment. Brain biopsy is required for definitive diagnosis. The objective of this study was to characterize the clinical and histopathological features of brain biopsies in small-vessel cPACNS (SVcPACNS). Methods:: A single-center prospective cohort study of children diagnosed with cPACNS from 1998 to 2008 was performed. All patients with negative cerebral angiography and brain biopsy were included. Patient data were reviewed for clinical, laboratory, and radiological characteristics at presentation. Standardized brain biopsy review protocols were established, with independent analysis by 2 neuropathologists. Histopathology was correlated with collected clinical data. Results:: A total of 13 SVcPACNS patients were included. Ages ranged from 5 to 17 years. Presenting features included seizures (85%), headache (62%), and cognitive decline (54%). Brain biopsy confirmed SVcPACNS in 11 patients with intramural lymphocytic infiltrate. Two had nonspecific perivascular inflammation only. All 6 nonlesional biopsies yielded a diagnosis of SVcPACNS. Lack of specific histological features correlated with prolonged time to biopsy, prior steroid treatment, and inadequate specimen sampling. Interpretation:: In children presenting with new onset severe headaches, seizures, or cognitive decline, SVcPACNS and brain biopsy should be considered. Lesional biopsies are preferred; however, nonlesional biopsies may succeed in yielding the diagnosis. Steroid treatment prior to biopsy and inadequate biopsy sampling may obscure the diagnosis in true cases of SVcPACNS. ANN NEUROL 2010;68:602-610 [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
38. Telomerase Inhibition as a Novel Therapy for Pediatric Ependymoma.
- Author
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Wong, Vincent C.H., Morrison, Andrew, Tabori, Uri, and Hawkins, Cynthia E.
- Subjects
BRAIN tumors ,TUMORS in children ,TELOMERASE ,DNA damage ,TUMOR growth - Abstract
Ependymomas are the third most common pediatric brain tumor with an overall survival of ∼50%. Recently, we showed that telomerase [human telomerase reverse transcriptase (hTERT)] expression is a predictor of poor outcome in pediatric ependymoma. Thus, we hypothesized that ependymomas with functional telomerase may behave more aggressively and that these patients may benefit from anti-telomerase therapy. To address our hypothesis, we investigated the effect of telomerase inhibition on primary ependymoma cells harvested at the time of surgery, as no animal models or established cell lines are readily available for this tumor. The cells were characterized for glial fibrillary acidic protein (GFAP) and hTERT expression, initial telomere length and telomerase activity. They were then subjected to telomerase inhibition (MST-312, 1 µM) and tested for effects on cell viability (MTT assay), proliferation (MIB-1), apoptosis (cleaved caspase 3) and DNA damage (γH2AX). After 72 h of telomerase inhibition, primary ependymoma cells showed a significant decrease in cell number ( P < 0.001), accompanied by increased DNA damage (γH2AX expression) ( P < 0.01) and decreased proliferative index (MIB-1) ( P < 0.01). Half showed an increase in apoptosis (cleaved caspase 3). These data suggest that telomerase inhibition may be an effective adjuvant therapy in pediatric ependymoma, potentially inducing tumor growth arrest in the short term, independent of telomere shortening. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
39. Diagnosis of limb-girdle muscular dystrophy 2A by immunohistochemical techniques.
- Author
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Kolski, Hanna K., Hawkins, Cynthia, Zatz, Mayana, De Paula, Flavia, Biggar, Doug, Alman, Ben, and Vajsar, Jiri
- Subjects
- *
IMMUNOHISTOCHEMISTRY techniques , *NEUROMUSCULAR diseases , *IMMUNOCHEMISTRY , *MUSCULAR dystrophy , *DIAGNOSIS - Abstract
The Western blot technique is currently the standard detection method for suspected limb girdle muscular dystrophy (LGMD) 2A (calpainopathy). This is the first report in the English literature of the successful application of immunohistochemical techniques to support a diagnosis of LGMD 2A. This approach is straightforward and appears to be reasonably specific. We propose that immunohistochemical methods should be re-evaluated for the screening of undiagnosed patients with suspected LGMD 2A. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
40. Characterization and transformation potential of 'Synthetic' astrocytes differentiated from murine embryonic stem cells.
- Author
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Kamnasaran, Deepak, Hawkins, Cynthia, and Guha, Abhijit
- Published
- 2008
- Full Text
- View/download PDF
41. Congenital Glioblastoma: A Clinicopathologic and Genetic Analysis.
- Author
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Brat, Daniel J., Shehata, Bahig M., Castellano-Sanchez, Amilcar A., Hawkins, Cynthia, Yost, Robert B., Greco, Claudia, Mazewski, Claire, Janss, Anna, Ohgaki, Hiroko, and Perry, Arie
- Subjects
GLIOBLASTOMA multiforme ,GLIOMAS ,BRAIN tumors ,TUMORS in children ,GENETIC disorders ,MEDICAL genetics - Abstract
Congenital central nervous system (CNS) tumors are uncommon, accounting for 1% of all childhood brain tumors. They present clinically either at birth or within the first 3 months. Glioblastoma (GBM) only rarely occurs congenitally and has not been fully characterized. We examined clinicopathologic features and genetic alterations of six congenital GBMs. Tumors were seen by neuroimaging as large, complex cerebral hemispheric masses. All showed classic GBM histopathology, including diffuse infiltration, dense cellularity, GFAP-positivity, high mitotic activity, endothelial proliferation and pseudopalisading necrosis. Neurosurgical procedures and adjuvant therapies varied. Survivals ranged from 4 days to 7.5 years; two of the three long-term survivors received chemotherapy, whereas the three short-term survivors did not. Paraffin-embedded tissue sections were used for FISH analysis of EGFR, chromosomes 9p21 ( p16/CDKN2A) and 10q ( PTEN/DMBT1); sequencing of PTEN and TP53; and immunohistochemistry for EGFR and p53. We uncovered 10q deletions in two cases. No EGFR amplifications, 9p21 deletions, or mutations of TP53 or PTEN were noted; however, nuclear p53 immunoreactivity was strong in 5/6 cases. Tumors were either minimally immunoreactive (n = 3) or negative (n = 3) for EGFR. We conclude that congenital GBMs show highly variable survivals. They are genetically distinct from their adult counterparts and show a low frequency of known genetic alterations. Nonetheless, the strong nuclear expression of p53 in these and other pediatric GBMs could indicate that p53 dysregulation is important to tumorigenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
42. Pilomyxoid astrocytoma in a patient with neurofibromatosis.
- Author
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Khanani, Muhammad Faisal, Hawkins, Cynthia, Shroff, Manohar, Dirks, Peter, Capra, Michael, Burger, P.C., and Bouffet, Eric
- Published
- 2006
- Full Text
- View/download PDF
43. Patients with primary brain tumors as organ donors: Case report and review of the literature.
- Author
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Punnett, Angela S., McCarthy, Lisa J., Dirks, Peter B., Hawkins, Cynthia, and Bouffet, Eric
- Published
- 2004
- Full Text
- View/download PDF
44. Indolent course of brainstem tumors with K27M‐H3.3 mutation.
- Author
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Baroni, Lorena V., Solano‐Paez, Palma, Nobre, Liana, Michaeli, Orli, Hawkins, Cynthia, Laughlin, Suzanne, Bartels, Ute, Ramaswamy, Vijay, and Bouffet, Eric
- Published
- 2020
- Full Text
- View/download PDF
45. Indolent course of brainstem tumors with K27M-H3.3 mutation.
- Author
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Baroni, Lorena V, Solano-Paez, Palma, Nobre, Liana, Michaeli, Orli, Hawkins, Cynthia, Laughlin, Susanne, Bartels, Ute, Ramaswamy, Vijay, Bouffet, Eric, and Laughlin, Suzanne
- Published
- 2019
- Full Text
- View/download PDF
46. cIMPACT-NOW (the consortium to inform molecular and practical approaches to CNS tumor taxonomy): a new initiative in advancing nervous system tumor classification.
- Author
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Louis, David N., Aldape, Ken, Brat, Daniel J., Capper, David, Ellison, David W., Hawkins, Cynthia, Paulus, Werner, Perry, Arie, Reifenberger, Guido, Figarella‐Branger, Dominique, Wesseling, Pieter, Batchelor, Tracy T., Gregory Cairncross, J., Pfister, Stefan M., Rutkowski, Stefan, Weller, Michael, Wick, Wolfgang, and von Deimling, Andreas
- Subjects
NEUROLOGY conferences ,CENTRAL nervous system ,TUMORS ,TAXONOMY ,MOLECULAR neurobiology - Published
- 2017
- Full Text
- View/download PDF
47. Repeat irradiation for children with supratentorial high-grade glioma.
- Author
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Tsang, Derek S., Oliveira, Carol, Bouffet, Eric, Hawkins, Cynthia, Ramaswamy, Vijay, Yee, Ryan, Tabori, Uri, Bartels, Ute, Huang, Annie, Millar, Barbara‐Ann, Crooks, Bruce, Bowes, Lynette, Zelcer, Shayna, Laperriere, Normand, and Millar, Barbara-Ann
- Published
- 2019
- Full Text
- View/download PDF
48. Central nervous system abnormalities in two cases with neonatal Marfan syndrome with novel mutations in the fibrillin-1 gene.
- Author
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Barnett CP, Wilson GJ, Chiasson DA, Gross GJ, Hinek A, Hawkins C, and Chitayat D
- Subjects
- Autopsy, DNA Mutational Analysis, Fatal Outcome, Female, Fibrillin-1, Fibrillins, Humans, Infant, Male, Central Nervous System abnormalities, Marfan Syndrome genetics, Microfilament Proteins genetics, Mutation
- Published
- 2010
- Full Text
- View/download PDF
49. Angiography-negative primary central nervous system vasculitis in children: a newly recognized inflammatory central nervous system disease.
- Author
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Benseler SM, deVeber G, Hawkins C, Schneider R, Tyrrell PN, Aviv RI, Armstrong D, Laxer RM, and Silverman ED
- Subjects
- Adolescent, Aspirin therapeutic use, Azathioprine therapeutic use, Child, Child, Preschool, Cyclophosphamide therapeutic use, Drug Therapy, Combination, Female, Humans, Immunosuppressive Agents therapeutic use, Magnetic Resonance Imaging, Prednisone therapeutic use, Treatment Outcome, Vasculitis, Central Nervous System drug therapy, Brain pathology, Cerebral Angiography, Vasculitis, Central Nervous System diagnosis
- Abstract
Inflammatory central nervous system (CNS) diseases in childhood comprise a wide spectrum of heterogeneous conditions. We studied 4 children with primary CNS vasculitis in whom results of magnetic resonance imaging studies were abnormal but results of conventional angiography were normal. We determined that angiography-negative, biopsy-confirmed primary small-vessel CNS vasculitis is a previously unrecognized distinct disease entity in children. The diagnosis must be considered in a child with a progressive, acquired diffuse or focal neurologic deficit, even if the results of conventional angiography are normal. A lesional brain biopsy is required to confirm the diagnosis. Use of immunosuppressive therapy plus aspirin leads to an excellent neurologic outcome.
- Published
- 2005
- Full Text
- View/download PDF
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