المؤلفون: Kalachi, Kourosh, Thomas, Cheddhi J., Savoca, Paul

المصدر: Gastro Hep Advances ; ISSN 2772-5723

الإتاحة: https://doi.org/10.1016/j.gastha.2024.03.010Test
https://api.elsevier.com/content/article/PII:S2772572324000414?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2772572324000414?httpAccept=text/plainTest

المؤلفون: Chen, Hui, Thomas, Cheddhi, Munoz, Felipe Andres, Alexandrescu, Sanda, Horbinski, Craig M, Olar, Adriana, McGuone, Declan, Camelo-Piragua, Sandra, Wang, Lu, Pentsova, Elena, Phillips, Joanna, Aldape, Kenneth, Chen, Wen, Iafrate, A John, Chi, Andrew S, Zagzag, David, Golfinos, John G, Placantonakis, Dimitris G, Rosenblum, Marc, Ohman-Strickland, Pamela, Hameed, Meera, Snuderl, Matija

المصدر: Neuro-Oncology. 21(9)

مصطلحات موضوعية: Cancer, Clinical Research, Adolescent, Adult, Aged, Aged, 80 and over, Aneuploidy, Brain Neoplasms, Chemotherapy, Adjuvant, Child, Chromosomal Instability, Chromosome Deletion, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 19, Female, Humans, In Situ Hybridization, Fluorescence, Isocitrate Dehydrogenase, Male, Middle Aged, Neoadjuvant Therapy, Neurosurgical Procedures, Oligodendroglioma, Prognosis, Progression-Free Survival, Radiotherapy, Adjuvant, Survival Rate, Young Adult, 1p/19q codeletion, glioma, oligodendroglioma, polysomy, Neurosciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis

الوصف: BackgroundChromosomal instability is associated with earlier progression in isocitrate dehydrogenase (IDH)-mutated astrocytomas. Here we evaluated the prognostic significance of polysomy in gliomas tested for 1p/19q status.MethodsWe analyzed 412 histologic oligodendroglial tumors with use of 1p/19q testing at 8 institutions from 1996 to 2013; fluorescence in situ hybridization (FISH) for 1p/19q was performed. Polysomy was defined as more than two 1q and 19p signals in cells. Tumors were divided into groups on the basis of their 1p/19q status and polysomy and were compared for progression-free survival (PFS) and overall survival (OS).ResultsIn our cohort, 333 tumors (81%) had 1p/19q loss; of these, 195 (59%) had concurrent polysomy and 138 (41%) lacked polysomy, 79 (19%) had 1p/19q maintenance; of these, 30 (38%) had concurrent polysomy and 49 (62%) lacked polysomy. In agreement with prior studies, the group with 1p/19q loss had significantly better PFS and OS than did the group with 1p/19q maintenance (P < 0.0001 each). Patients with 1p/19q loss and polysomy showed significantly shorter PFS survival than patients with 1p/19q codeletion only (P < 0.0001), but longer PFS and OS than patients with 1p/19q maintenance (P < 0.01 and P < 0.0001). There was no difference in survival between tumors with >30% polysomic cells and those with

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4sd2j0m5Test

المؤلفون: Dang, Danielle D., Gong, Andrew D., Thomas, Cheddhi, Vyas, Nilesh, Moores, Leon E.

المصدر: 33rd Annual Meeting North American Skull Base Society ; Journal of Neurological Surgery Part B: Skull Base ; ISSN 2193-634X

الإتاحة: https://doi.org/10.1055/s-0044-1780147Test

المؤلفون: Chen, Hao, Judkins, Jonathon, Thomas, Cheddhi, Wu, Meijing, Khoury, Laith, Benjamin, Carolina G, Pacione, Donato, Golfinos, John G, Kumthekar, Priya, Ghamsari, Farhad, Chen, Li, Lein, Pamela, Chetkovich, Dane M, Snuderl, Matija, Horbinski, Craig

المصدر: Neurology. 88(19)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Epilepsy, Neurodegenerative, Rare Diseases, Neurosciences, Cancer, Brain Cancer, Brain Disorders, Neurological, Action Potentials, Animals, Brain Neoplasms, Cells, Cultured, Cerebral Cortex, Chromosome Deletion, Chromosomes, Human, Pair 1, Female, Glioma, Glutarates, Humans, Isocitrate Dehydrogenase, Male, Middle Aged, Mutation, Neoplasm Grading, Neurons, Rats, Sprague-Dawley, Retrospective Studies, Seizures, Cognitive Sciences, Neurology & Neurosurgery, Clinical sciences

الوصف: ObjectiveBecause the d-2-hydroxyglutarate (D2HG) product of mutant isocitrate dehydrogenase 1 (IDH1mut) is released by tumor cells into the microenvironment and is structurally similar to the excitatory neurotransmitter glutamate, we sought to determine whether IDH1mut increases the risk of seizures in patients with glioma, and whether D2HG increases the electrical activity of neurons.MethodsThree WHO grade II-IV glioma cohorts from separate institutions (total N = 712) were retrospectively assessed for the presence of preoperative seizures and tumor location, WHO grade, 1p/19q codeletion, and IDH1mut status. Rat cortical neurons were grown on microelectrode arrays, and their electrical activity was measured before and after treatment with exogenous D2HG, in the presence or absence of the selective NMDA antagonist, AP5.ResultsPreoperative seizures were observed in 18%-34% of IDH1 wild-type (IDH1wt) patients and in 59%-74% of IDH1mut patients (p < 0.001). Multivariable analysis, including WHO grade, 1p/19q codeletion, and temporal lobe location, showed that IDH1mut was an independent correlate with seizures (odds ratio 2.5, 95% confidence interval 1.6-3.9, p < 0.001). Exogenous D2HG increased the firing rate of cultured rat cortical neurons 4- to 6-fold, but was completely blocked by AP5.ConclusionsThe D2HG product of IDH1mut may increase neuronal activity by mimicking the activity of glutamate on the NMDA receptor, and IDH1mut gliomas are more likely to cause seizures in patients. This has rapid translational implications for the personalized management of tumor-associated epilepsy, as targeted IDH1mut inhibitors may improve antiepileptic therapy in patients with IDH1mut gliomas.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/5163372pTest
https://escholarship.org/content/qt5163372p/qt5163372p.pdfTest

المؤلفون: Tang, Karen, Kurland, David, Vasudevaraja, Varshini, Serrano, Jonathan, Delorenzo, Michael, Radmanesh, Alireza, Thomas, Cheddhi, Spino, Marissa, Gardner, Sharon, Allen, Jeffrey C, Nicolaides, Theodore, Osorio, Diana S, Finlay, Jonathan L, Boué, Daniel R, Snuderl, Matija

المساهمون: Friedberg Charitable Foundation, Making Headway Foundation, NYU CTSA, National Center for Advancing Translational Sciences, NIH

المصدر: Journal of Neuropathology & Experimental Neurology ; volume 79, issue 8, page 880-890 ; ISSN 0022-3069 1554-6578

مصطلحات موضوعية: Cellular and Molecular Neuroscience, Neurology (clinical), Neurology, General Medicine, Pathology and Forensic Medicine

الوصف: Pleomorphic xanthoastrocytoma (PXA) is a rare type of brain tumor that affects children and young adults. Molecular prognostic markers of PXAs remain poorly established. Similar to gangliogliomas, PXAs show prominent immune cell infiltrate, but its composition also remains unknown. In this study, we correlated DNA methylation and BRAF status with clinical outcome and explored the tumor microenvironment. We performed DNA methylation in 21 tumor samples from 18 subjects with a histological diagnosis of PXA. MethylCIBERSORT was used to deconvolute the PXA microenvironment by analyzing the associated immune cell-types. Median age at diagnosis was 16 years (range 7–32). At median follow-up of 30 months, 3-year and 5-year overall survival was 73% and 71%, respectively. Overall survival ranged from 1 to 139 months. Eleven out of 18 subjects (61%) showed disease progression. Progression-free survival ranged from 1 to 89 months. Trisomy 7 and CDKN2A/B (p16) homozygous deletion did not show any association with overall survival (p = 0.67 and p = 0.74, respectively). Decreased overall survival was observed for subjects with tumors lacking the BRAF V600E mutation (p = 0.02). PXAs had significantly increased CD8 T-cell epigenetic signatures compared with previously profiled gangliogliomas (p = 0.0019). The characterization of immune cell-types in PXAs may have implications for future development of immunotherapy.

الإتاحة: https://doi.org/10.1093/jnen/nlaa051Test
https://academic.oup.com/jnen/article-pdf/79/8/880/40419873/jnen_79_8_880.pdfTest

المؤلفون: Friedman, Daniel, Kannan, Kasthuri, Faustin, Arline, Shroff, Seema, Thomas, Cheddhi, Heguy, Adriana, Serrano, Jonathan, Snuderl, Matija, Devinsky, Orrin

المصدر: npj Genomic Medicine ; volume 3, issue 1 ; ISSN 2056-7944

مصطلحات موضوعية: Genetics (clinical), Genetics, Molecular Biology

الوصف: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality in young adults. The exact mechanisms are unknown but death often follows a generalized tonic–clonic seizure. Proposed mechanisms include seizure-related respiratory, cardiac, autonomic, and arousal dysfunction. Genetic drivers underlying SUDEP risk are largely unknown. To identify potential SUDEP risk genes, we compared whole-exome sequences (WES) derived from formalin-fixed paraffin embedded surgical brain specimens of eight epilepsy patients who died from SUDEP with seven living controls matched for age at surgery, sex, year of surgery and lobe of resection. We compared identified variants from both groups filtering known polymorphisms from publicly available data as well as scanned for epilepsy and candidate SUDEP genes. In the SUDEP cohort, we identified mutually exclusive variants in genes involved in µ-opiod signaling, gamma-aminobutyric acid (GABA) and glutamate-mediated synaptic signaling, including ARRB2 , ITPR1 , GABRR2 , SSTR5 , GRIK1 , CTNAP2 , GRM8 , GNAI2 and GRIK5 . In SUDEP patients we also identified variants in genes associated with cardiac arrhythmia, including KCNMB1 , KCNIP1 , DPP6 , JUP , F2 , and TUBA3D , which were not present in living epilepsy controls. Our data shows that genomic analysis of brain tissue resected for seizure control can identify potential genetic biomarkers of SUDEP risk.

الإتاحة: https://doi.org/10.1038/s41525-018-0048-5Test
https://www.nature.com/articles/s41525-018-0048-5.pdfTest
https://www.nature.com/articles/s41525-018-0048-5Test

المؤلفون: Garcia, Mekka R, Feng, Yang, Vasudevaraja, Varshini, Galbraith, Kristyn, Serrano, Jonathan, Thomas, Cheddhi, Radmanesh, Alireza, Hidalgo, Eveline T, Harter, David H, Allen, Jeffrey C, Gardner, Sharon L, Osorio, Diana S, William, Christopher M, Zagzag, David, Boué, Daniel R, Snuderl, Matija

المصدر: Journal of Neuropathology & Experimental Neurology ; volume 81, issue 11, page 865-872 ; ISSN 0022-3069 1554-6578

الوصف: Diffuse spinal cord gliomas (SCGs) are rare tumors associated with a high morbidity and mortality that affect both pediatric and adult populations. In this retrospective study, we sought to characterize the clinical, pathological, and molecular features of diffuse SCG in 22 patients with histological and molecular analyses. The median age of our cohort was 23.64 years (range 1–82) and the overall median survival was 397 days. K27M mutation was significantly more prevalent in males compared to females. Gross total resection and chemotherapy were associated with improved survival, compared to biopsy and no chemotherapy. While there was no association between tumor grade, K27M status (p = 0.366) or radiation (p = 0.772), and survival, males showed a trend toward shorter survival. K27M mutant tumors showed increased chromosomal instability and a distinct DNA methylation signature.

الإتاحة: https://doi.org/10.1093/jnen/nlac075Test
https://academic.oup.com/jnen/article-pdf/81/11/865/46558037/nlac075.pdfTest

المؤلفون: Huse, Jason T., Snuderl, Matija, Jones, David T. W., Brathwaite, Carole D., Altman, Nolan, Lavi, Ehud, Saffery, Richard, Sexton-Oates, Alexandra, Blumcke, Ingmar, Capper, David, Karajannis, Matthias A., Benayed, Ryma, Chavez, Lukas, Thomas, Cheddhi, Serrano, Jonathan, Borsu, Laetitia, Ladanyi, Marc, Rosenblum, Marc K.

المساهمون: Sontag Foundation, Friedberg Charitable Foundation, National Cancer Institute

المصدر: Acta Neuropathologica ; volume 133, issue 3, page 417-429 ; ISSN 0001-6322 1432-0533

مصطلحات موضوعية: Cellular and Molecular Neuroscience, Neurology (clinical), Pathology and Forensic Medicine

الإتاحة: https://doi.org/10.1007/s00401-016-1639-9Test

المؤلفون: Orillac, Cordelia, Thomas, Cheddhi, Dastagirzada, Yosef, Hidalgo, Eveline Teresa, Golfinos, John G., Zagzag, David, Wisoff, Jeffrey H., Karajannis, Matthias A., Snuderl, Matija

المساهمون: Friedberg Charitable Foundation, Rachel Molly Markoff Foundation

المصدر: Acta Neuropathologica Communications ; volume 4, issue 1 ; ISSN 2051-5960

مصطلحات موضوعية: Cellular and Molecular Neuroscience, Neurology (clinical), Pathology and Forensic Medicine

الإتاحة: https://doi.org/10.1186/s40478-016-0361-0Test

المؤلفون: Segal, Devorah, Thomas, Cheddhi, Bowman, Christopher, Kannan, Kasthuri, Wang, Shiyang, Heguy, Adriana, Liechty, Benjamin, Jones, David T. W., Hovestadt, Volker, Pfister, Stefan M., Karajannis, Matthias, Snuderl, Matija

المصدر: Neuro-Oncology ; volume 18, issue suppl_6, page vi118-vi118 ; ISSN 1522-8517 1523-5866

مصطلحات موضوعية: Cancer Research, Neurology (clinical), Oncology

الإتاحة: https://doi.org/10.1093/neuonc/now212.493Test
http://academic.oup.com/neuro-oncology/article-pdf/18/suppl_6/vi118/9643614/now212.493.pdfTest