11 results on '"Hawkins, Cynthia"'
Search Results
2. 101 Re-Irradiation for Children with Recurrent Supratentorial High-Grade Glioma
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Oliveira, Carol, Laperriere, Normand J., Bouffet, Eric, Hawkins, Cynthia, Ramaswamy, Vijay, Yee, Ryan, Tabori, Uri, Bartels, Ute, Huang, Annie, Millar, Barbara-Ann, Crooks, Bruce, Bowes, Lynette, Zelcer, Shayna, and Tsang, Derek S.
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- 2019
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3. Management and outcome of chordomas in the pediatric population: The Hospital for Sick Children experience and review of the literature.
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Tsitouras, Vassilios, Wang, Shelly, Dirks, Peter, Drake, James, Bouffet, Eric, Hawkins, Cynthia, Laughlin, Suzanne, and Rutka, James T.
- Abstract
Chordomas are tumors arising from remnants of the embryological notochord, most commonly found in the spheno-occipital, spinal, or sacro-coccygeal areas. They are rare tumors in the pediatric population and are challenging to manage due to their difficult accessibility, proximity to important anatomy and extension into adjacent structures. We report a series of 10 children treated for chordoma at The Hospital for Sick Children focusing on their surgery, adjuvant therapy and long-term outcomes. A retrospective review involving patient charts, radiographic imaging, and pathology slides was performed for 10 chordoma patients during the period from 1987–2015. Important variables, including patient demographics, chordoma location, presentation, imaging characteristics, pathology subtype, treatment options, and long-term outcome were analysed. The series consists of seven girls and three boys with cranial or upper cervical spine chordomas. One patient presented with an extradural left cerebellopontine angle chordoma demonstrating aggressive and dedifferentiated features, which, to our knowledge, has not been previously described in the literature. All patients received surgical resection followed by photon or proton radiotherapy. Four patients with chondroid or atypical pathology also received chemotherapeutic adjuvants. All patients with classical pathology achieved favourable outcome, while the four patients with atypical pathology progressed quickly despite aggressive therapy, suggesting that pathology subtype is a crucial prognostic factor. This study summarizes 30 years of surgical and adjuvant therapy experience in a large academic center for pediatric chordoma patients. Patient outcomes were dependent on pathology subtype, and a multidisciplinary approach involving surgery, radiotherapy, and chemotherapy can be considered on an individual basis. [ABSTRACT FROM AUTHOR]
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- 2016
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4. Medulloblastoma Arises from the Persistence of a Rare and Transient Sox2+ Granule Neuron Precursor.
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Selvadurai, Hayden J., Luis, Erika, Desai, Kinjal, Lan, Xiaoyang, Vladoiu, Maria C., Whitley, Owen, Galvin, Ciaran, Vanner, Robert J., Lee, Lilian, Whetstone, Heather, Kushida, Michelle, Nowakowski, Tomasz, Diamandis, Phedias, Hawkins, Cynthia, Bader, Gary, Kriegstein, Arnold, Taylor, Michael D., and Dirks, Peter B.
- Abstract
Medulloblastoma (MB) is a neoplasm linked to dysregulated cerebellar development. Previously, we demonstrated that the Sonic Hedgehog (SHH) subgroup grows hierarchically, with Sox2
+ cells at the apex of tumor progression and relapse. To test whether this mechanism is rooted in a normal developmental process, we studied the role of Sox2 in cerebellar development. We find that the external germinal layer (EGL) is derived from embryonic Sox2+ precursors and that the EGL maintains a rare fraction of Sox2+ cells during the first postnatal week. Through lineage tracing and single-cell analysis, we demonstrate that these Sox2+ cells are within the Atoh1+ lineage, contribute extensively to adult granule neurons, and resemble Sox2+ tumor cells. Critically, constitutive activation of the SHH pathway leads to their aberrant persistence in the EGL and rapid tumor onset. We propose that failure to eliminate this rare but potent developmental population is the tumor initiation mechanism in SHH-subgroup MB. • A rare and transient population of Sox2+ cells is identified in the developing EGL • These stem-like Sox2+ cells contribute extensively to the granule lineage • Constitutive activation of SHH in Sox2+ cells leads to their abnormal persistence • Medulloblastoma arises from the sustained hierarchical output from these Sox2+ cells Selvadurai et al. demonstrate that the developing cerebellar external germinal layer contains a transient population of more primitive cells expressing Sox2. Aberrant activation of the SHH signaling pathway in these cells causes persistent hierarchical growth, leading to medulloblastoma. [ABSTRACT FROM AUTHOR]- Published
- 2020
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5. Sa2045 Tumor Spectrum, Diagnostic Tools and Survival in Patients With Biallelic Mismatch Repair Gene Deficiency (BMMRD) Syndrome: Report From the International BMMRD Consortium.
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Durno, Carol, Aronson, Melyssa, Campbell, Brittany, Zhukova, Nataliya, Shlien, Adam, Reddy, Alyssa T., Hawkins, Cynthia, Malkin, David, Bouffet, Eric, Mason, Gary, Hansford, Jordan, Peterson, Lindsay, Osborn, Michael, Sullivan, Michael, Taylor, Michael, Jabado, Nada, Demore, Nancy, Dvir, Rina, Elhasid, Ronit, and Farah, Roula
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- 2016
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6. Lethal Disorder of Mitochondrial Fission Caused by Mutations in DNM1L.
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Yoon, Grace, Malam, Zeenat, Paton, Tara, Marshall, Christian R., Hyatt, Ella, Ivakine, Zhenya, Scherer, Stephen W., Lee, Kyong-Soon, Hawkins, Cynthia, Cohn, Ronald D., and Finding of Rare Disease Genes (FORGE) in Canada Consortium Steering Committee
- Abstract
We describe two infants with hypotonia, absent respiratory effort, and giant mitochondria in neurons due to compound heterozygosity for 2 nonsense mutations of DNM1L. DNM1L has a critical role in regulating mitochondrial morphology and function. This observation confirms the central role of mitochondrial fission to normal human development. [ABSTRACT FROM AUTHOR]
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- 2016
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7. Pathological Findings of a Subependymal Giant Cell Astrocytoma Following Treatment With Rapamycin.
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Cheng, Sylvia, Hawkins, Cynthia, Taylor, Michael D., and Bartels, Ute
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ASTROCYTOMAS , *HYDROCEPHALUS , *RAPAMYCIN , *HERITABILITY , *MTOR protein , *CLINICAL trials , *THERAPEUTICS - Abstract
Background Tuberous sclerosis complex is a heritable multisystem disorder associated with genes involved in the formation of a tumor-suppressor complex acting through the Ras homologue enriched in brain protein to limit activation of the mammalian target of rapamycin complex I. Mutations in these genes result in enhanced mammalian target of rapamycin signaling and may cause neurological manifestations including brain tubers, subependymal nodules, and subependymal giant cell astrocytomas. These astrocytomas are tumors that arise near the foramen of Monro and may lead to obstructive hydrocephalus. Standard therapy has been surgical resection. More recently, mammalian target of rapamycin inhibitor, everolimus, has been approved for treatment after demonstration of efficacy in prospective clinical trials. Methods We report a 15 year-old girl with tuberous sclerosis complex who proceeded to surgical resection of her subependymal giant cell astrocytoma after 3 months of treatment with mammalian target of rapamycin inhibition. We compared her subependymal giant cell astrocytoma tissue specimen with 12 untreated subependymal giant cell astrocytomas accessed from The Hospital for Sick Children in Toronto, Canada. Results This girl's histopathological findings were consistent with subependymal giant cell astrocytomas with no exposure to mammalian target of rapamycin inhibitors. There were no major differences identified on immunohistochemistry at targets downstream of mammalian target of rapamycin complex 1 or in neighboring signaling pathways. The majority of cells were reactive to glial fibrillary acidic protein, mitogen-activated protein kinase, phospho-S6, caspase 3 (95% positivity), and NP-1. Conclusion In this one individual, rapamycin therapy did not change the histopathological characteristics of subependymal giant cell astrocytoma. Mammalian target of rapamycin inhibition involves complex signaling pathways inducing subependymal giant cell astrocytoma shrinkage. However, its effect is not easily characterized within tumor tissue. [ABSTRACT FROM AUTHOR]
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- 2015
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8. Phenotypic and genotypic characterisation of biallelic mismatch repair deficiency (BMMR-D) syndrome.
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Durno, Carol A., Sherman, Philip M., Aronson, Melyssa, Malkin, David, Hawkins, Cynthia, Bakry, Doua, Bouffet, Eric, Gallinger, Steven, Pollett, Aaron, Campbell, Brittany, and Tabori, Uri
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DIAGNOSIS of hereditary nonpolyposis colorectal cancer , *HEREDITARY nonpolyposis colorectal cancer , *LYNCH syndrome II , *DIFFERENTIAL diagnosis , *PHENOTYPES , *GENOTYPES , *GENETICS , *DIAGNOSIS - Abstract
Lynch syndrome, the most common inherited colorectal cancer syndrome in adults, is an autosomal dominant condition caused by heterozygous germ-line mutations in DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2 . Inheriting biallelic (homozygous) mutations in any of the MMR genes results in a different clinical syndrome termed biallelic mismatch repair deficiency (BMMR-D) that is characterised by gastrointestinal tumours, skin lesions, brain tumours and haematologic malignancies. This recently described and under-recognised syndrome can present with adenomatous polyps leading to early-onset small bowel and colorectal adenocarcinoma. An important clue in the family history that suggests underling BMMR-D is consanguinity. Interestingly, pedigrees of BMMR-D patients typically show a paucity of Lynch syndrome cancers and most parents are unaffected. Therefore, a family history of cancers is often non-contributory. Detection of BMMR-D can lead to more appropriate genetic counselling and the implementation of targeted surveillance protocols to achieve earlier tumour detection that will allow surgical resection. This review describes an approach for diagnosis and management of these patients and their families. [ABSTRACT FROM AUTHOR]
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- 2015
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9. Molecular subgroups of atypical teratoid rhabdoid tumours in children: an integrated genomic and clinicopathological analysis.
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Torchia, Jonathon, Picard, Daniel, Lafay-Cousin, Lucie, Hawkins, Cynthia E, Kim, Seung-Ki, Letourneau, Louis, Ra, Young-Shin, Ho, King Ching, Chan, Tiffany Sin Yu, Sin-Chan, Patrick, Dunham, Christopher P, Yip, Stephen, Ng, Ho-keung, Lu, Jian-Qiang, Albrecht, Steffen, Pimentel, José, Chan, Jennifer A, Somers, Gino R, Zielenska, Maria, and Faria, Claudia C
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TERATOMA , *TUMORS in children , *HETEROGENEITY , *GENOMES , *COHORT analysis , *TUMOR treatment - Abstract
Summary Background Rhabdoid brain tumours, also called atypical teratoid rhabdoid tumours, are lethal childhood cancers with characteristic genetic alterations of SMARCB1/hSNF5 . Lack of biological understanding of the substantial clinical heterogeneity of these tumours restricts therapeutic advances. We integrated genomic and clinicopathological analyses of a cohort of patients with atypical teratoid rhabdoid tumours to find out the molecular basis for clinical heterogeneity in these tumours. Methods We obtained 259 rhabdoid tumours from 37 international institutions and assessed transcriptional profiles in 43 primary tumours and copy number profiles in 38 primary tumours to discover molecular subgroups of atypical teratoid rhabdoid tumours. We used gene and pathway enrichment analyses to discover group-specific molecular markers and did immunohistochemical analyses on 125 primary tumours to evaluate clinicopathological significance of molecular subgroup and ASCL1-NOTCH signalling. Findings Transcriptional analyses identified two atypical teratoid rhabdoid tumour subgroups with differential enrichment of genetic pathways, and distinct clinicopathological and survival features. Expression of ASCL1, a regulator of NOTCH signalling, correlated with supratentorial location (p=0·004) and superior 5-year overall survival (35%, 95% CI 13–57, and 20%, 6–34, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0·033) in 70 patients who received multimodal treatment. ASCL1 expression also correlated with superior 5-year overall survival (34%, 7–61, and 9%, 0–21, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0·001) in 39 patients who received only chemotherapy without radiation. Cox hazard ratios for overall survival in patients with differential ASCL1 enrichment treated with chemotherapy with or without radiation were 2·02 (95% CI 1·04–3·85; p=0·038) and 3·98 (1·71–9·26; p=0·001). Integrated analyses of molecular subgroupings with clinical prognostic factors showed three distinct clinical risk groups of tumours with different therapeutic outcomes. Interpretation An integration of clinical risk factors and tumour molecular groups can be used to identify patients who are likely to have improved long-term radiation-free survival and might help therapeutic stratification of patients with atypical teratoid rhabdoid tumours. Funding C17 Research Network, Genome Canada, b.r.a.i.n.child, Mitchell Duckman, Tal Doron and Suri Boon foundations. [ABSTRACT FROM AUTHOR]
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- 2015
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10. Ongoing issues with the management of children with Constitutional Mismatch Repair Deficiency syndrome.
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Chahine, Nassim Abi, Farhat, Hussein, Campbell, Brittany, Zhukova, Nataliya, Durno, Carol, Aronson, Melyssa, Hawkins, Cynthia, Bouffet, Eric, Tabori, Uri, Farah, Roula A., and Maalouf, Farid
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RADIATION tolerance , *EARLY detection of cancer , *CANCER , *SYNDROMES , *DYNAMIC testing ,CENTRAL nervous system tumors - Abstract
Constitutional Mismatch Repair Deficiency (CMMRD) is a rare cancer predisposition syndrome, presenting in childhood, in which affected patients develop various malignancies such as hematological, gastrointestinal and central nervous system tumors. Although guidelines are being increasingly developed for surveillance and early detection of cancers in affected families, there are no clear recommendations regarding choice of therapy and very scarce information about tolerance to chemotherapy and radiation in these patients. We report the pedigree of a consanguineous family with four affected children. Although clinical and molecular tests confirm CMMRD, genetic testing revealed heterogeneous mutations. The index case developed severe toxicity from therapy for glioblastoma and T-cell leukemia and died from an infection while in complete remission. His sister developed a malignant brain tumor while undergoing surveillance for a low grade brain lesion and is still undergoing follow-up. This family illustrates the difficulties and opportunities with challenging diagnosis, surveillance and choice of therapy for children with CMMRD and the need for increased awareness and more information about this rare but important syndrome. [ABSTRACT FROM AUTHOR]
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- 2019
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11. Evaluation of SNP Genomic Microarray Analysis as an Alternative to FISH Analysis of Pediatric Solid Tumors.
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Arnoldo, Anthony, Stavropoulos, James, Thorner, Paul, Hawkins, Cynthia, Somers, Gino R., and Shago, Mary
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FLUORESCENCE in situ hybridization , *DNA copy number variations , *CHROMOSOME abnormalities , *NERVOUS system tumors , *STATISTICAL correlation , *GENE amplification , *PATIENTS , *PROGNOSIS - Published
- 2015
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