Search

Your search keyword '"Ramaswamy, V"' showing total 56 results
Start Over Author "Ramaswamy, V" Database OpenAIRE
56 results on '"Ramaswamy, V"'

1. Digital Document Analysis Using Weighted Score Convolutional Neural Network and Arc Factored Graph Based Dependency Parsing

Author

Rekha D Rekha D and Ramaswamy V Ramaswamy V

Abstract

Digital document analysis is one where software analysts review documents for assessing an appraisal theme. Digital document analysis can be utilized for obtaining available documents in order to extract relevant data. Most of the research work focuses on a semi-supervised based framework for better parsing performance and traditional statistical setting. However, an inappropriate selection during digital documents analysis may lead to entire process being falsified there by reducing the overall accuracy. To address this issue, in our work, a novel method called, Weighted Score Convolutional Network and Arc-factored Graph-based Dependency Parsing (WSCN-AGDP) is proposed. WSCN-AGDP is split into two sections. First section is concerned with the extraction of relevant features (i.e., words from sentences) by employing Stouffer’s Weighted Score-based Convolutional Neural Network model. In the second section, using the extracted features, Graph-based Dependency Parsing is performed by utilizing Spearman Correlated Arc-Factored model. Four indices were calculated namely, digital document parsing time, parsing overhead, false positive rate and precision are being used to quantitatively assess and rate the algorithms. Different document sizes acquired from Reuters-21578 dataset are considered. Experiments have been conducted to analyze the methods.

Published
2022

2. Developing Digital Twins for Earth Systems: Purpose, Requisites, and Benefits

Author

Rao, Yuhan, Redmon, Rob, Dale, Kirstine, Haupt, Sue E., Hopkinson, Aaron, Bostrom, Ann, Boukabara, Sid, Geenen, Thomas, Hall, David M., Smith, Benjamin D., Niyogi, Dev, Ramaswamy, V., and Kihn, Eric A.

Subjects
FOS: Computer and information sciences, Physics - Physics and Society, Physics - Atmospheric and Oceanic Physics, Atmospheric and Oceanic Physics (physics.ao-ph), FOS: Physical sciences, Applications (stat.AP), Physics and Society (physics.soc-ph), Statistics - Applications
Abstract

The accelerated change in our planet due to human activities has led to grand societal challenges including health crises, intensified extreme weather events, food security, environmental injustice, etc. Digital twin systems combined with emerging technologies such as artificial intelligence and edge computing provide opportunities to support planning and decision-making to address these challenges. Digital twins for Earth systems (DT4ESs) are defined as the digital representation of the complex integrated Earth system including both natural processes and human activities. They have the potential to enable a diverse range of users to explore what-if scenarios across spatial and temporal scales to improve our understanding, prediction, mitigation, and adaptation to grand societal challenges. The 4th NOAA AI Workshop convened around 100 members who are developing or interested in participating in the development of DT4ES to discuss a shared community vision and path forward on fostering a future ecosystem of interoperable DT4ES. This paper summarizes the workshop discussions around DT4ES. We first defined the foundational features of a viable digital twins for Earth system that can be used to guide the development of various use cases of DT4ES. Finally, we made practical recommendations for the community on different aspects of collaboration in order to enable a future ecosystem of interoperable DT4ES, including equity-centered use case development, community-driven investigation of interoperability for DT4ES, trust-oriented co-development, and developing a community of practice., Comment: This whitepaper is an outcome of the 4th NOAA AI Workshop

Published
2023
Full Text
View/download PDF

3. Bevacizumab for NF2-associated vestibular schwannomas of childhood and adolescence

Author

Renzi S, Michaeli O, Salvador-Hernandez H, Alderete D, Ponce NF, Zapotocky M, Hansford JR, Malalasekera VS, Toledano H, Maguire B, Bouffet E, Ramaswamy V, and Baroni LV

Subjects
bevacizumab, genetic structures, brain tumors, otorhinolaryngologic diseases, NF2, vestibular schwannomas
Abstract

Seventeen children at six institutions with neurofibromatosis type 2 (NF2)-related vestibular schwannomas received bevacizumab. Eight of the 13 patients with initial hearing loss (61%) showed objective hearing improvement within six months of treatment. No patients showed hearing deterioration during therapy; however, only two patients showed objective radiological response. Seven of eight patients had tumor progression or worsening hearing loss upon cessation of treatment. Bevacizumab was well tolerated with no patients discontinuing therapy. Bevacizumab appears to postpone hearing loss in childhood NF2-associated vestibular schwannomas, but responses are not durable, suggesting that either longer maintenance therapy or new strategies are required.

Published
2020

4. Treatment response of CNS high-grade neuroepithelial tumors with MN1 alteration

Author

Baroni LV, Rugilo C, Lubieniecki F, Sampor C, Freytes C, Nobre L, Hansford JR, Malalasekera VS, Zapotocky M, Dodgshun A, Martinez OC, Morales-La Madrid A, Lavarino C, Suñol M, Rutkowski S, Schuller U, Bouffet E, Ramaswamy V, and Alderete D

Subjects
neuroepithelial tumor, astroblastoma, CNS HGNET-MN1, MN1, ependymoma
Abstract

Central nervous system high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1) is a rare recently described entity. Fourteen CNS HGNET-MN1 patients were identified using genome-wide methylation arrays/RT-PCR across seven institutions. All patients had surgery (gross total resection: 10; subtotal resection: four) as initial management followed by observation alone in three patients, followed by radiotherapy in eight patients (focal: five; craniospinal: two; CyberKnife: one) and systemic chemotherapy in three patients. Seven patients relapsed; five local and two metastatic, despite adjuvant radiotherapy, of which three died. Treatment of CNS HGNET-MN1 remains a major treatment challenge despite aggressive surgical resections and upfront radiotherapy, warranting new approaches to this rare malignancy.

Published
2020

5. Erratum: A Hematogenous Route for Medulloblastoma Leptomeningeal Metastases (S0092867418301156 (2018) 172(5) (1050–1062.e14) (S0092867418301156) (10.1016/j.cell.2018.01.038))

Author

Garzia L., Kijima N., Morrissy A. S., De Antonellis P., Guerreiro-Stucklin A., Holgado B. L., Wu X., Wang X., Parsons M., Zayne K., Manno A., Kuzan-Fischer C., Nor C., Donovan L. K., Liu J., Qin L., Garancher A., Liu K. -W., Mansouri S., Luu B., Thompson Y. Y., Ramaswamy V., Peacock J., Farooq H., Skowron P., Shih D. J. H., Li A., Ensan S., Robbins C. S., Cybulsky M., Mitra S., Ma Y., Moore R., Mungall A., Cho Y. -J., Weiss W. A., Chan J. A., Hawkins C. E., Massimino M., Jabado N., Zapotocky M., Sumerauer D., Bouffet E., Dirks P., Tabori U., Sorensen P. H. B., Brastianos P. K., Aldape K., Jones S. J. M., Marra M. A., Woodgett J. R., Wechsler-Reya R. J., Fults D. W., Taylor M. D., Garzia, L., Kijima, N., Morrissy, A. S., De Antonellis, P., Guerreiro-Stucklin, A., Holgado, B. L., Wu, X., Wang, X., Parsons, M., Zayne, K., Manno, A., Kuzan-Fischer, C., Nor, C., Donovan, L. K., Liu, J., Qin, L., Garancher, A., Liu, K. -W., Mansouri, S., Luu, B., Thompson, Y. Y., Ramaswamy, V., Peacock, J., Farooq, H., Skowron, P., Shih, D. J. H., Li, A., Ensan, S., Robbins, C. S., Cybulsky, M., Mitra, S., Ma, Y., Moore, R., Mungall, A., Cho, Y. -J., Weiss, W. A., Chan, J. A., Hawkins, C. E., Massimino, M., Jabado, N., Zapotocky, M., Sumerauer, D., Bouffet, E., Dirks, P., Tabori, U., Sorensen, P. H. B., Brastianos, P. K., Aldape, K., Jones, S. J. M., Marra, M. A., Woodgett, J. R., Wechsler-Reya, R. J., Fults, D. W., and Taylor, M. D.

Abstract

(Cell 172, 1050–1062; February 22, 2018) It has come to our attention that in preparing the final version of the manuscript, we made a mistake in the legend for Figure 6. The figure includes 4 major panels labeled A, B, C and D, and we inadvertently included descriptions for panels A, B, C, D, and E. The information in the Figure 6E legend describes panel 6D and should have been labeled as such, and the text labeled 6D should have been deleted. The error has been corrected online, and we apologize for any confusion we may have caused.

Published
2018

6. A New Paradigm for Diagnosing Contributions to Model Aerosol Forcing Error

Author

Jones, AL, Feldman, DR, Freidenreich, S, Paynter, D, Ramaswamy, V, Collins, WD, and Pincus, R

Subjects
Climate Action, Meteorology & Atmospheric Sciences, Physics::Atmospheric and Oceanic Physics
Abstract

©2017. The Authors. A new paradigm in benchmark absorption-scattering radiative transfer is presented that enables both the globally averaged and spatially resolved testing of climate model radiation parameterizations in order to uncover persistent sources of biases in the aerosol instantaneous radiative effect (IRE). A proof of concept is demonstrated with the Geophysical Fluid Dynamics Laboratory AM4 and Community Earth System Model 1.2.2 climate models. Instead of prescribing atmospheric conditions and aerosols, as in prior intercomparisons, native snapshots of the atmospheric state and aerosol optical properties from the participating models are used as inputs to an accurate radiation solver to uncover model-relevant biases. These diagnostic results show that the models' aerosol IRE bias is of the same magnitude as the persistent range cited (~1 W/m2) and also varies spatially and with intrinsic aerosol optical properties. The findings underscore the significance of native model error analysis and its dispositive ability to diagnose global biases, confirming its fundamental value for the Radiative Forcing Model Intercomparison Project.

Published
2017

7. combining satellite measurements and numerical flood prediction models to save life and properties from flooding

Author

Saleh, Firas, Biancamaria, Sylvain, Garambois, Pierre-André, Ramaswamy, V., Finaud-Guyot, Pascal, Laboratoire d'études en Géophysique et océanographie spatiales (LEGOS), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, and Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDU.STU.HY]Sciences of the Universe [physics]/Earth Sciences/Hydrology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2017

10. Cytogenetic prognostication within medulloblastoma subgroups

Author

Shih, DJH, Northcott, PA, Remke, M, Korshunov, A, Ramaswamy, V, Kool, M, Luu, B, Yao, Y, Wang, X, Dubuc, AM, Garzia, L, Peacock, J, Mack, SC, Wu, X, Rolider, A, Morrissy, AS, Cavalli, FMG, Jones, DTW, Zitterbart, K, Faria, CC, Schüller, U, Kren, L, Kumabe, T, Tominaga, T, Ra, YS, Garami, M, Hauser, P, Chan, JA, Robinson, S, Bognár, L, Klekner, A, Saad, AG, Liau, LM, Albrecht, S, Fontebasso, A, Cinalli, G, De Antonellis, P, Zollo, M, Cooper, MK, Thompson, RC, Bailey, S, Lindsey, JC, Di Rocco, C, Massimi, L, Michiels, EMC, Scherer, SW, Phillips, JJ, Gupta, N, Fan, X, Muraszko, KM, Vibhakar, R, Eberhart, CG, Fouladi, M, Lach, B, Jung, S, Wechsler-Reya, RJ, Fèvre-Montange, M, Jouvet, A, Jabado, N, Pollack, IF, Weiss, WA, Lee, JY, Cho, BK, Kim, SK, Wang, KC, Leonard, JR, Rubin, JB, De Torres, C, Lavarino, C, Mora, J, Cho, YJ, Tabori, U, Olson, JM, Gajjar, A, Packer, RJ, Rutkowski, S, Pomeroy, SL, French, PJ, Kloosterhof, NK, Kros, JM, Van Meir, EG, Clifford, SC, Bourdeaut, F, Delattre, O, Doz, FF, Hawkins, CE, Malkin, D, and Grajkowska, WA

Subjects
Male, Adolescent, Kruppel-Like Transcription Factors, Zinc Finger Protein Gli2, Risk Assessment, Proto-Oncogene Proteins c-myc, Cytogenetics, Young Adult, Risk Factors, Predictive Value of Tests, Biomarkers, Tumor, Humans, Hedgehog Proteins, Oncology & Carcinogenesis, Child, In Situ Hybridization, Fluorescence, Proportional Hazards Models, Chromosomes, Human, Pair 14, Oncology And Carcinogenesis, Chromosomes, Human, Pair 11, Gene Expression Profiling, Nuclear Proteins, Reproducibility of Results, Infant, Prognosis, Gene Expression Regulation, Neoplastic, Wnt Proteins, Tissue Array Analysis, Child, Preschool, Female, Medulloblastoma
Abstract

Purpose: Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Patients and Methods: Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Results: Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Conclusion: Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials. © 2014 by American Society of Clinical Oncology.

Published
2014

11. Contribution of Local and Remote Anthropogenic Aerosols to the 20th century Weakening of the South Asian Monsoon

Author

Bollasina, Massimo, Ming, Yi, Ramaswamy, V., Schwarzkopf, M. Daniel, and Naik, Vaishali

Subjects
respiratory system, complex mixtures
Abstract

The late twentieth century response of the South Asian monsoon to changes in anthropogenic aerosols from local (i.e., South Asia) and remote (i.e., outside South Asia) sources was investigated using historical simulations with a state-of-the-art climate model. The observed summertime drying over India is replaced by widespread wettening once local aerosol emissions are kept at preindustrial levels while all the other forcings evolve. Constant remote aerosol emissions partially suppress the precipitation decrease. While predominant precipitation changes over India are thus associated with local aerosols, remote aerosols contribute as well, especially in favoring an earlier monsoon onset in June and enhancing summertime rainfall over the northwestern regions. Conversely, temperature and near-surface circulation changes over South Asia are more effectively driven by remote aerosols. These changes are reflected into northward cross-equatorial anomalies in the atmospheric energy transport induced by both local and, to a greater extent, remote aerosols.

Published
2014

12. TERT promoter mutations are highly recurrent in SHH subgroup medulloblastoma

Author

Liau, Linda, Weiss, William, Remke, M, Ramaswamy, V, Peacock, J, Shih, DJH, Koelsche, C, Northcott, PA, Hill, N, Cavalli, FMG, Kool, M, and Wang, X

Subjects
stomatognathic diseases, neoplasms, nervous system diseases
Abstract

Telomerase reverse transcriptase (TERT) promoter mutations were recently shown to drive telomerase activity in various cancer types, including medulloblastoma. However, the clinical and biological implications of TERT mutations in medulloblastoma have not

Published
2013

13. Earlier onset of the Indian monsoon in the late twentieth century: The role of anthropogenic aerosols

Author

Bollasina, Massimo A., Ming, Yi, and Ramaswamy, V.

Abstract

The impact of the late twentieth century increase of anthropogenic aerosols on the Indian monsoon onset was investigated with a state-of-the-art climate model with fully interactive aerosols and chemistry. We find that aerosols are likely responsible for the observed earlier onset, resulting in enhanced June precipitation over most of India. This shift is preceded by strong aerosol forcing over the Bay of Bengal and Indochina, mostly attributable to the direct effect, resulting in increased atmospheric stability that inhibits the monsoon migration in May. The adjusted atmospheric circulation leads to thermodynamic changes over the northwestern continental region, including increased surface temperature and near-surface moist static energy, which support a stronger June flow and, facilitated by a relative warming of the Indian Ocean, a vigorous northwestward precipitation shift. These findings underscore the importance of dynamical feedbacks and of regional land-surface processes for the aerosol-monsoon link.

Published
2013

14. Subgroup-specific structural variation across 1,000 medulloblastoma genomes

Author

Northcott, PA, Shih, DJH, Peacock, J, Garzia, L, Sorana Morrissy, A, Zichner, T, Stútz, AM, Korshunov, A, Reimand, J, Schumacher, SE, Beroukhim, R, Ellison, DW, Marshall, CR, Lionel, AC, MacK, S, Dubuc, A, Yao, Y, Ramaswamy, V, Luu, B, Rolider, A, Cavalli, FMG, Wang, X, Remke, M, Wu, X, Chiu, RYB, Chu, A, Chuah, E, Corbett, RD, Hoad, GR, Jackman, SD, Li, Y, Lo, A, Mungall, KL, Ming Nip, K, Qian, JQ, Raymond, AGJ, Thiessen, N, Varhol, RJ, Birol, I, Moore, RA, Mungall, AJ, Holt, R, Kawauchi, D, Roussel, MF, Kool, M, Jones, DTW, Witt, H, Fernandez-L, A, Kenney, AM, Wechsler-Reya, RJ, Dirks, P, Aviv, T, Grajkowska, WA, Perek-Polnik, M, Haberler, CC, Delattre, O, Reynaud, SS, Doz, FF, Pernet-Fattet, SS, Cho, BK, Kim, SK, Wang, KC, Scheurlen, W, Eberhart, CG, Fèvre-Montange, M, Jouvet, A, Pollack, IF, Fan, X, Muraszko, KM, Yancey Gillespie, G, Di Rocco, C, Massimi, L, Michiels, EMC, Kloosterhof, NK, French, PJ, Kros, JM, Olson, JM, Ellenbogen, RG, Zitterbart, K, Kren, L, Thompson, RC, and Cooper, MK

Subjects
Oncogene Proteins, Fusion, DNA Copy Number Variations, Genome, Human, General Science & Technology, NF-kappa B, Genes, myc, Proteins, Nerve Tissue Proteins, Genomics, Translocation, Genetic, Transforming Growth Factor beta, Gene Duplication, Genomic Structural Variation, MD Multidisciplinary, Humans, Hedgehog Proteins, RNA, Long Noncoding, Cerebellar Neoplasms, Carrier Proteins, Child, Medulloblastoma, Signal Transduction
Abstract

Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy. © 2012 Macmillan Publishers Limited. All rights reserved.

Published
2012

18. Encryption Quality Analysis and Security Evaluation of CAST-128 Algorithm and its Modified Version using Digital Images

Author

Krishnamurthy, G. N. and Ramaswamy, V.

Subjects
FOS: Computer and information sciences, Computer Science - Cryptography and Security, Cryptography and Security (cs.CR), Computer Science::Cryptography and Security
Abstract

this paper demonstrates analysis of well known block cipher CAST-128 and its modified version using avalanche criterion and other tests namely encryption quality, correlation coefficient, histogram analysis and key sensitivity tests., Comment: 6Pages

Published
2010
Full Text
View/download PDF

19. Climate-Ozone Connections

Author

Baldwin, M., Dameris, M., Austin, J., Bekki, S., Bregman, B., Butchart, N., Cordero, E., Gillett, N., Graf, H.-F., Cranier, C., Kinnison, D., Lal, S., Peter, T., Randel, W., Scinocca, J., Shindell, D., Struthers, H., Takahashi, M., Thompson, D., Battisti, D., Braesicke, P., Garcia, R., Haynes, P., Manzini, E., Matthes, Katja, Pitari, G., Ramaswamy, V., Rosenlof, K., Santer, B., Scott, R., Stenke, A., and Timmreck, C.

Published
2007

20. GFDL's CM2 Global Coupled Climate Models Part 1: Formulation and Simulation Characteristics

Author

Delworth, Thomas L., Broccoli, Anthony J., Rosati, Anthony, Stouffer, Ronald J., Balaji, V., Beesley, John A., Cooke, William F., Dixon, Keith W., Dunne, John, Dunne, K. A., Durachta, Jeffrey W., Findell, Kirsten L., Ginoux, Paul, Gnanadesikan, Anand, Gordon, C. T., Griffies, Stephen M., Gudgel, Rich, Harrison, Matthew J., Held, Isaac M., Hemler, Richard S., Horowitz, Larry W., Klein, Stephen A., Knutson, Thomas R., Kushner, Paul J., Langenhorst, Amy R., Lee, Hyun-Chul, Lin, Shian-Jiann, Lu, Jian, Malyshev, Sergey L., Milly, P. C. D., Ramaswamy, V., Russell, Joellen, Daniel Schwarzkopf, M., Schwarzkopf, M. Daniel, Shevliakova, Elena, Sirutis, Joseph J., Spelman, Michael J., Stern, William F., Winton, Michael, Wittenberg, Andrew T., Wyman, Bruce, Zeng, Fanrong, and Zhang, Rong

Subjects
Physics::Atmospheric and Oceanic Physics, Physics::Geophysics
Abstract

The formulation and simulation characteristics of two new global coupled climate models developed at NOAA's Geophysical Fluid Dynamics Laboratory (GFDL) are described. The models were designed to simulate atmospheric and oceanic climate and variability from the diurnal time scale through multicentury climate change, given our computational constraints. In particular, an important goal was to use the same model for both experimental seasonal to interannual forecasting and the study of multicentury global climate change, and this goal has been achieved. Tw o versions of the coupled model are described, called CM2.0 and CM2.1. The versions differ primarily in the dynamical core used in the atmospheric component, along with the cloud tuning and some details of the land and ocean components. For both coupled models, the resolution of the land and atmospheric components is 2° latitude × 2.5° longitude; the atmospheric model has 24 vertical levels. The ocean resolution is 1° in latitude and longitude, with meridional resolution equatorward of 30° becoming progressively finer, such that the meridional resolution is 1/3° at the equator. There are 50 vertical levels in the ocean, with 22 evenly spaced levels within the top 220 m. The ocean component has poles over North America and Eurasia to avoid polar filtering. Neither coupled model employs flux adjustments. The co ntrol simulations have stable, realistic climates when integrated over multiple centuries. Both models have simulations of ENSO that are substantially improved relative to previous GFDL coupled models. The CM2.0 model has been further evaluated as an ENSO forecast model and has good skill (CM2.1 has not been evaluated as an ENSO forecast model). Generally reduced temperature and salinity biases exist in CM2.1 relative to CM2.0. These reductions are associated with 1) improved simulations of surface wind stress in CM2.1 and associated changes in oceanic gyre circulations; 2) changes in cloud tuning and the land model, both of which act to increase the net surface shortwave radiation in CM2.1, thereby reducing an overall cold bias present in CM2.0; and 3) a reduction of ocean lateral viscosity in the extratropics in CM2.1, which reduces sea ice biases in the North Atlantic. Both models have be en used to conduct a suite of climate change simulations for the 2007 Intergovernmental Panel on Climate Change (IPCC) assessment report and are able to simulate the main features of the observed warming of the twentieth century. The climate sensitivities of the CM2.0 and CM2.1 models are 2.9 and 3.4 K, respectively. These sensitivities are defined by coupling the atmospheric components of CM2.0 and CM2.1 to a slab ocean model and allowing the model to come into equilibrium with a doubling of atmospheric CO2. The output from a suite of integrations conducted with these models is freely available online (see http://nomads.gfdl.noaa.gov/).

Published
2006

22. Summary for Policymakers

Author

Albritton, D., Allen, M., Baede, A., Church, J., Cubasch, U., Xiaosu, D., Yihui, D., Ehhalt, D., Folland, C., Giorgi, F., Gregory, J., Griggs, D., Haywood, J., Hewitson, B., Houghton, J., House, J., Hulme, M., Isaksen, I., Jaramillo, V., Jayaraman, A., Johnson, C., Joos, F., Joussaume, S., Karl, T., Karoly, D., Kheshgi, H., Le Quéré, C., Maskell, K., Mata, L., McAvaney, B., McFarland, M., Mearns, L., Meehl, G., Meira-Filho, L., Meleshko, V., Mitchell, J., Moore, B., Mugara, R., Noguer, M., Nyenzi, B., Oppenheimer, M., Penner, J., Pollonais, S., Prather, M., Prentice, I., Ramaswamy, V., Ramirez-Rojas, A., Raper, S., Salinger, M., Scholes, R., Solomon, S., Stocker, T., Stone, J., Stouffer, R., Trenberth, K., Wang, M., Watson, R., Yap, K., Zillman, J., and Houghton, J.

Published
2001

27. Thin Layer Chromatographic Determination of Ctrinin

Author

H. M. Stahr and Ramaswamy V Chalam

Subjects
Materials science, Chromatography, Thin layer chromatographic, General Chemistry
Abstract

A thin layer chromatographic (TLC) method is described for the determination of citrinin in feeds. Citrinin is extracted from feed with methanol and water, the mixture is made alkaline with 10% sodium carbonate, and the aqueous solution is filtered and extracted with chloroform to remove most of the interfering materials. The aqueous layer is acidified with 2N HCl and extracted with chloroform. The chloroform extract is concentrated and spotted on a thin layer chromatographic (TLC) plate which is developed in chloroform-acetoneethanol- water (60+40+10+1). The citrinin is viewed under ultraviolet light after TLC. Either visual or fiuorodensitometric quantitation is used. Recoveries of citrinin from various feed samples spiked at levels of 2.0–5 μg/g were 75–92%. The proposed method can detect 0.5 μg/g feed, including corn, silage, ready mixed feeds, and feed pellets.

Published
1979

28. Effect of Crop Residue on Blue-Green Algae Growth in Wetland Rice

Author

Ramaswamy, V. and Sankaran, S.

Subjects
Wetland Rice, Crop Residues, Cyanobacteria
Abstract

This article 'Effect of Crop Residue on Blue-Green Algae Growth in Wetland Rice' appeared in the International Rice Research Newsletter series, created by the International Rice Research Institute (IRRI). The primary objective of this publication was to expedite communication among scientists concerned with the development of improved technology for rice and for rice based cropping systems. This publication will report what scientists are doing to increase the production of rice in as much as this crop feeds the most densely populated and land scarce nations in the world.

Published
1983
Full Text
View/download PDF

29. Effect of Rice Crop Residue Management on Weed Growth in Lowland Rice

Author

Ramaswamy, V., Sankaran, S., and Palaniappan, S. P.

Subjects
Crop Residues, Weeds, Lowland Rice
Abstract

This article 'Effect of Rice Crop Residue Management on Weed Growth in Lowland Rice' appeared in the International Rice Research Newsletter series, created by the International Rice Research Institute (IRRI). The primary objective of this publication was to expedite communication among scientists concerned with the development of improved technology for rice and for rice based cropping systems. This publication will report what scientists are doing to increase the production of rice in as much as this crop feeds the most densely populated and land scarce nations in the world.

Published
1984
Full Text
View/download PDF

30. BI-21BRAF MUTATION AND CDKN2A DELETIONS DEFINE A CLINICALLY DISTINCT SUBGROUP OF CHILDHOOD SECONDARY HIGH GRADE GLIOMA

Author

Mistry M, Zhukova N, Merico D, Rakopoulos P, Krishnatry R, Shago M, Stavropoulos J, Ray P, Mangerel J, Marc Remke, Buczkowicz P, Ramaswamy V, Rutka J, Dirks P, Taylor M, Bouffet E, Malkin D, Huang A, Hawkins C, and Tabori U

Subjects
Abstracts, Cancer Research, Oncology, Neurology (clinical)
Abstract

PURPOSE: Pediatric secondary high grade glioma (sHGG), which result from malignant transformation of low grade glioma (PLGG), are a poorly understood group of tumors with devastating outcomes. PATIENTS AND METHODS: We performed a population-based study combined with long-term follow-up of PLGG that transformed to sHGG. Exonic-sequencing and copy number alterations were investigated on a discovery cohort, followed by detailed genetic analysis of all tumors. Clinical and outcome data analysis of a genetically distinct subgroup was performed. RESULTS: sHGG were observed in 28/888 (3.2%) patients treated in Southern Ontario for PLGG with a median latency of 2.74 years (range, 0.18-20.3 years). sHGG were characterized by a high somatic mutation load (23 per genome). Alterations in chromatin modifying genes and major telomere maintenance pathways were observed in 57% and 54% of sHGG respectively. However, specific mutations in IDH1, H3F3A G34 and ATRX were extremely rare. The most recurrent somatic alterations were the oncogenic BRAF V600E mutation and deletion of the tumor suppressor gene CDKN2A, observed in 39% and 57% of sHGG respectively. Importantly, all BRAF V600E and 80% of CDKN2A alterations could be traced to the patient-matched PLGG counterparts. These early alterations were rarely observed in non-transformed PLGG (p < 0.0001) and primary childhood high grade glioma (p = 0.0023). The BRAF mutant sHGG subgroup was characterized by longer latency periods to transformation than non-BRAF mutant sHGG (median 6.59 versus 1.62 years; p < 0.0001). Furthermore, 5-year overall survival of children with BRAF mutant and wild-type PLGG that transformed were 75% ± 15% and 29% ± 12% respectively (p = 0.024). CONCLUSION: BRAF V600E mutations and CDKN2A deletions constitute a clinically distinct subtype of sHGG. The prolonged course to transformation provides a window of opportunity for aggressive surgical interventions, targeted therapy against oncogenic BRAF, and extended surveillance to potentially mitigate the devastating transformation event.

32. The new GFDL global atmosphere and land model AM2-LM2: Evaluation with prescribed SST simulations

Author

Anderson, J. L., Balaji, V., Anthony Broccoli, Cooke, W. F., Delworth, T. L., Dixon, K. W., Donner, L. J., Dunne, K. A., Freidenreich, S. M., Garner, S. T., Gudgel, R. G., Gordon, C. T., Held, I. M., Hemler, R. S., Horowitz, L. W., Klein, S. A., Knutson, T. R., Kushner, P. J., Langenhost, A. R., Lau, N. -C, Liang, Z., Malyshev, S. L., Milly, P. C. D., Nath, M. J., Ploshay, J. J., Ramaswamy, V., Schwarzkopf, M. D., Shevliakova, E., Sirutis, J. J., Soden, B. J., Stern, W. F., Thompson, L. A., Wilson, R. J., Wittenberg, A. T., and Wyman, B. L.

33. Summary for Policymakers

Author

Alexander, L. V., Allen, S. K., Bindoff, N. L., Breon, F. M., Church, J. A., Cubasch, U., Emori, S., Forster, P., Friedlingstein, P., Gillett, N., Gregory, J. M., Hartmann, D. L., Jansen, E., Kirtman, B., Knutti, R., Kanikicharla, K. K., Lemke, P., Marotzke, J., Masson-Delmotte, V., Meehl, G. A., Mokhov, II, Piao, S. L., Plattner, G. K., Qin, D. H., Ramaswamy, V., Randall, D., Rhein, M., Rojas, M., Sabine, C., Shindell, D., Stocker, T. F., Talley, L. D., Vaughan, D. G., Xie, S. P., Allen, M. R., Boucher, O., Chambers, D., Jens Hesselbjerg Christensen, Ciais, P., Clark, P. U., Collins, M., Comiso, J. C., Menezes, V. V., Feely, R. A., Fichefet, T., Fiore, A. M., Flato, G., Fuglestvedt, J., Hegerl, G., Hezel, P. J., Johnson, G. C., Kaser, G., Kattsov, V., Kennedy, J., Tank, Amgk, Le Quere, C., Myhre, G., Osborn, T., Payne, A. J., Perlwitz, J., Power, S., Prather, M., Rintoul, S. R., Rogelj, J., Rusticucci, M., Schulz, M., Sedlacek, J., Stott, P. A., Sutton, R., Thorne, P. W., and Wuebbles, D.

37. Study of effect of removal of shiftrows and mixcolumns stages of AES and AES-KDS on their encryption quality and hence security

Author

Krishnamurthy Ningappa and Ramaswamy, V.

Subjects
Hardware_ARITHMETICANDLOGICSTRUCTURES
Abstract

This paper demonstrates the results when either Shiftrows stage or Mixcolumns stage and when both the stages are omitted in the well known block cipher Advanced Encryption Standard(AES) and its modified version AES with Key Dependent S-box(AES-KDS), using avalanche criterion and other tests namely encryption quality, correlation coefficient, histogram analysis and key sensitivity tests.

38. The new GFDL global atmosphere and land model AM2-LM2: Evaluation with prescribed SST simulations

Author

Anderson, Jl, Balaji, V., Broccoli, Aj, Cooke, Wf, Delworth, Tl, Dixon, Kw, Donner, Lj, Dunne, Ka, Freidenreich, Sm, Garner, St, Gudgel, Rg, Gordon, Ct, Held, Im, Hemler, Rs, Horowitz, Lw, Klein, Sa, Knutson, Tr, Kushner, Pj, Langenhost, Ar, Lau, Nc, Liang, Z., Malyshev, Sl, Milly, Pcd, Nath, Mj, Jeffrey Ploshay, Ramaswamy, V., Schwarzkopf, Md, Shevliakova, E., Sirutis, Jj, Soden, Bj, Stern, Wf, Thompson, La, Wilson, Rj, Wittenberg, At, Wyman, Bl, and Gfdl, Global Atmospheric Model Dev

39. Assessment of twentieth-century regional surface temperature trends using the GFDL CM2 coupled models

Author

Knutson, T. R., Delworth, T. L., Dixon, K. W., Held, I. M., Lu, J., Ramaswamy, V., Schwarzkopf, M. D., Georgiy Lvovich Stenchikov, and Stouffer, R. J.

Abstract

Historical climate simulations of the period 1861–2000 using two new Geophysical Fluid Dynamics Laboratory (GFDL) global climate models (CM2.0 and CM2.1) are compared with observed surface tem-peratures. All-forcing runs include the effects of changes in well-mixed greenhouse gases, ozone, sulfates, black and organic carbon, volcanic aerosols, solar flux, and land cover. Indirect effects of tropospheric aerosols on clouds and precipitation processes are not included. Ensembles of size 3 (CM2.0) and 5 (CM2.1) with all forcings are analyzed, along with smaller ensembles of natural-only and anthropogenic-only forcing, and multicentury control runs with no external forcing. Observed warming trends on the global scale and in many regions are simulated more realistically in the all-forcing and anthropogenic-only forcing runs than in experiments using natural-only forcing or no ex-ternal forcing. In the all-forcing and anthropogenic-only forcing runs, the model shows some tendency for too much twentieth-century warming in lower latitudes and too little warming in higher latitudes. Differ-ences in Arctic Oscillation behavior between models and observations contribute substantially to an un-derprediction of the observed warming over northern Asia. In the all-forcing and natural-only forcing runs, a temporary global cooling in the models during the 1880s not evident in the observed temperature records is volcanically forced. El Niño interactions complicate comparisons of observed and simulated temperature records for the El Chichón and Mt. Pinatubo eruptions during the early 1980s and early 1990s. The simulations support previous findings that twentieth-century global warming has resulted from a combination of natural and anthropogenic forcing, with anthropogenic forcing being the dominant cause of the pronounced late-twentieth-century warming. The regional results provide evidence for an emergent anthropogenic warming signal over many, if not most, regions of the globe. The warming signal has emerged rather monotonically in the Indian Ocean/western Pacific warm pool during the past half-century. The tropical and subtropical North Atlantic and the tropical eastern Pacific are examples of regions where the anthropogenic warming signal now appears to be emerging from a background of more substantial mul-tidecadal variability. * UCAR Visiting Scientist.

43. Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma

Author

Anne Jouvet, Ana Gutiérrez-Fernández, Namal Abeysundara, Olivier Ayrault, Vijay Ramaswamy, Charles G. Eberhart, Jennifer A. Chan, Johan M. Kros, Xiaochong Wu, Sachin Kumar, Seung-Ki Kim, Maria C. Vladoiu, Noriyuki Kijima, Xose S. Puente, Ian F. Pollack, Robert J. Wechsler-Reya, Boleslaw Lach, Almos Klekner, Ander Diaz-Navarro, Claudia C. Faria, Lincoln Stein, Nicole Gauer, Enrique López-Aguilar, Nada Jabado, Amulya A. Nageswara Rao, Livia Garzia, David Malkin, Stefan M. Pfister, Jiannis Ragoussis, Maura Massimino, James M. Olson, Caterina Giannini, Hamza Farooq, Pim J. French, Florence M.G. Cavalli, Anna Goldenberg, John A. Calarco, Joshua B. Rubin, Maria Luisa Garrè, Betty Luu, László Bognár, Weifan Dong, Shimin Shuai, Antoine Forget, Jun Wang, Ichiyo Shibahara, Pasqualino De Antonellis, William A. Weiss, Marco A. Marra, Lola B. Chambless, Patryk Skowron, Wiesława Grajkowska, Jiao Zhang, Ali Momin, Erwin G. Van Meir, Michelle Fèvre-Montange, Rajeev Vibhakar, Ho Keung Ng, David Przelicki, Hiromichi Suzuki, Kyle Juraschka, Craig Daniels, A. Sorana Morrissy, Toshihiro Kumabe, Xi Huang, Wai Sang Poon, Swneke D. Bailey, Michael D. Taylor, Pathology, Neurology, Institut Curie, PSL Research University, CNRS UMR, INSERM, Orsay, France. 4Université Paris Sud, Université Paris- Saclay, CNRS UMR 3347, INSERM U1021, Orsay, France., Institut Curie [Paris], Suzuki H., Kumar S.A., Shuai S., Diaz-Navarro A., Gutierrez-Fernandez A., De Antonellis P., Cavalli F.M.G., Juraschka K., Farooq H., Shibahara I., Vladoiu M.C., Zhang J., Abeysundara N., Przelicki D., Skowron P., Gauer N., Luu B., Daniels C., Wu X., Forget A., Momin A., Wang J., Dong W., Kim S.-K., Grajkowska W.A., Jouvet A., Fevre-Montange M., Garre M.L., Nageswara Rao A.A., Giannini C., Kros J.M., French P.J., Jabado N., Ng H.-K., Poon W.S., Eberhart C.G., Pollack I.F., Olson J.M., Weiss W.A., Kumabe T., Lopez-Aguilar E., Lach B., Massimino M., Van Meir E.G., Rubin J.B., Vibhakar R., Chambless L.B., Kijima N., Klekner A., Bognar L., Chan J.A., Faria C.C., Ragoussis J., Pfister S.M., Goldenberg A., Wechsler-Reya R.J., Bailey S.D., Garzia L., Morrissy A.S., Marra M.A., Huang X., Malkin D., Ayrault O., Ramaswamy V., Puente X.S., Calarco J.A., Stein L., Taylor M.D., Repositório da Universidade de Lisboa, Suzuki, H., Kumar, S. A., Shuai, S., Diaz-Navarro, A., Gutierrez-Fernandez, A., De Antonellis, P., Cavalli, F. M. G., Juraschka, K., Farooq, H., Shibahara, I., Vladoiu, M. C., Zhang, J., Abeysundara, N., Przelicki, D., Skowron, P., Gauer, N., Luu, B., Daniels, C., Wu, X., Forget, A., Momin, A., Wang, J., Dong, W., Kim, S. -K., Grajkowska, W. A., Jouvet, A., Fevre-Montange, M., Garre, M. L., Nageswara Rao, A. A., Giannini, C., Kros, J. M., French, P. J., Jabado, N., Ng, H. -K., Poon, W. S., Eberhart, C. G., Pollack, I. F., Olson, J. M., Weiss, W. A., Kumabe, T., Lopez-Aguilar, E., Lach, B., Massimino, M., Van Meir, E. G., Rubin, J. B., Vibhakar, R., Chambless, L. B., Kijima, N., Klekner, A., Bognar, L., Chan, J. A., Faria, C. C., Ragoussis, J., Pfister, S. M., Goldenberg, A., Wechsler-Reya, R. J., Bailey, S. D., Garzia, L., Morrissy, A. S., Marra, M. A., Huang, X., Malkin, D., Ayrault, O., Ramaswamy, V., Puente, X. S., Calarco, J. A., Stein, L., Taylor, M. D., and Olivier, AYRAULT

Subjects
0301 basic medicine, Adult, Adolescent, RNA Splicing, [SDV]Life Sciences [q-bio], Biology, Article, 03 medical and health sciences, 0302 clinical medicine, GLI2, RNA, Small Nuclear, medicine, Humans, G%29+of+U1+spliceosomal+small+nuclear+RNAs+%28snRNAs%29%22">subgroups of medulloblastoma, recurrent hotspot mutations (r.3A>G) of U1 spliceosomal small nuclear RNAs (snRNAs), Hedgehog Proteins, Sonic hedgehog, Cerebellar Neoplasms, Gene, ComputingMilieux_MISCELLANEOUS, Medulloblastoma, Multidisciplinary, Cerebellar Neoplasm, Alternative splicing, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Alternative Splicing, 030104 developmental biology, PTCH1, RNA Splice Site, 030220 oncology & carcinogenesis, RNA splicing, Mutation, Cancer research, biology.protein, RNA Splice Sites, Hedgehog Protein, Small nuclear RNA, Human
Abstract

© The Author(s), under exclusive licence to Springer Nature Limited 2019, In cancer, recurrent somatic single-nucleotide variants-which are rare in most paediatric cancers-are confined largely to protein-coding genes1-3. Here we report highly recurrent hotspot mutations (r.3A>G) of U1 spliceosomal small nuclear RNAs (snRNAs) in about 50% of Sonic hedgehog (SHH) medulloblastomas. These mutations were not present across other subgroups of medulloblastoma, and we identified these hotspot mutations in U1 snRNA in only

Published
2019

44. Intertumoral Heterogeneity within Medulloblastoma Subgroups

Author

Luca Massimi, Caterina Giannini, Betty Luu, Cynthia Hawkins, Byung Kyu Cho, James T. Rutka, G. Yancey Gillespie, Timothy E. Van Meter, Almos Klekner, Young Shin Ra, Carolina Nor, Anna Goldenberg, Rajeev Vibhakar, Hideo Nakamura, Gaetano Finocchiaro, Massimo Zollo, John Peacock, Marta Perek-Polnik, Keren Isaev, Alvaro Lassaletta, Amulya A. Nageswara Rao, Florence M.G. Cavalli, Maura Massimino, Livia Garzia, Jüri Reimand, Charles G. Eberhart, Maryam Fouladi, Enrique López-Aguilar, Annie Huang, Cécile Faure-Conter, Gary D. Bader, Jaume Mora, Ho Keung Ng, James M. Olson, Jennifer A. Chan, Erwin G. Van Meir, Daniela Pretti da Cunha Tirapelli, Hamza Farooq, Fernando Chico Ponce de León, Linda M. Liau, Kay Ka Wai Li, Shenandoah Robinson, Anne Jouvet, Tomoko Shofuda, José Pimentel, Reid C. Thompson, Yuan Yao Thompson, Ian F. Pollack, Nada Jabado, Boleslaw Lach, Pim J. French, Joshua B. Rubin, Eric Bouffet, Alexandre Vasiljevic, Ali G. Saad, Michael K. Cooper, Satoru Osuka, Peter B. Dirks, Jaroslav Sterba, Johan M. Kros, Claudia C. Faria, Kyu-Chang Wang, Seung-Ki Kim, Shin Jung, Craig Daniels, A. Sorana Morrissy, Ladislav Rampášek, Andrew R. Hallahan, Sarah Leary, Wiesława Grajkowska, Uri Tabori, Marc Remke, Samer K. Elbabaa, Michael D. Taylor, Andrew S. Moore, Toshihiro Kumabe, Mario Perezpeña-Diazconti, Vijay Ramaswamy, Ronald L. Hamilton, Claudia M. Kuzan-Fischer, Marie Lise C. van Veelen, Helen Wheeler, Michal Zapotocky, Ji Yeoun Lee, David Shih, Jeffrey R. Leonard, Karel Zitterbart, Carlos Gilberto Carlotti, Steffen Albrecht, Jonathon Torchia, Peter Hauser, Ute Bartels, William A. Weiss, Sameer Agnihotri, Lola B. Chambless, Neurosurgery, Pathology, Neurology, Cavalli, Fmg, Remke, M, Rampasek, L, Peacock, J, Shih, Djh, Luu, B, Garzia, L, Torchia, J, Nor, C, Morrissy, A, Agnihotri, S, Thompson, Yy, Kuzan-Fischer, Cm, Farooq, H, Isaev, K, Daniels, C, Cho, Bk, Kim, Sk, Wang, Kc, Lee, Jy, Grajkowska, Wa, Perek-Polnik, M, Vasiljevic, A, Faure-Conter, C, Jouvet, A, Giannini, C, Nageswara Rao, Aa, Li, Kkw, Ng, Hk, Eberhart, Cg, Pollack, If, Hamilton, Rl, Gillespie, Gy, Olson, Jm, Leary, S, Weiss, Wa, Lach, B, Chambless, Lb, Thompson, Rc, Cooper, Mk, Vibhakar, R, Hauser, P, van Veelen, Mc, Kros, Jm, French, Pj, Ra, Y, Kumabe, T, López-Aguilar, E, Zitterbart, K, Sterba, J, Finocchiaro, G, Massimino, M, Van Meir, Eg, Osuka, S, Shofuda, T, Klekner, A, Zollo, M, Leonard, Jr, Rubin, Jb, Jabado, N, Albrecht, S, Mora, J, Van Meter, Te, Jung, S, Moore, A, Hallahan, Ar, Chan, Ja, Tirapelli, Dpc, Carlotti, Cg, Fouladi, M, Pimentel, J, Faria, Cc, Saad, Ag, Massimi, L, Liau, Lm, Wheeler, H, Nakamura, H, Elbabaa, Sk, Perezpeña-Diazconti, M, Chico Ponce de León, F, Robinson, S, Zapotocky, M, Lassaletta, A, Huang, Weiping, Hawkins, Ce, Tabori, U, Bouffet, E, Bartels, U, Dirks, Pb, Rutka, Jt, Bader, Gd, Reimand, J, Goldenberg, A, Ramaswamy, V, Taylor, Md, Cavalli F.M.G., Remke M., Rampasek L., Peacock J., Shih D.J.H., Luu B., Garzia L., Torchia J., Nor C., Morrissy A.S., Agnihotri S., Thompson Y.Y., Kuzan-Fischer C.M., Farooq H., Isaev K., Daniels C., Cho B.-K., Kim S.-K., Wang K.-C., Lee J.Y., Grajkowska W.A., Perek-Polnik M., Vasiljevic A., Faure-Conter C., Jouvet A., Giannini C., Nageswara Rao A.A., Li K.K.W., Ng H.-K., Eberhart C.G., Pollack I.F., Hamilton R.L., Gillespie G.Y., Olson J.M., Leary S., Weiss W.A., Lach B., Chambless L.B., Thompson R.C., Cooper M.K., Vibhakar R., Hauser P., van Veelen M.-L.C., Kros J.M., French P.J., Ra Y.S., Kumabe T., Lopez-Aguilar E., Zitterbart K., Sterba J., Finocchiaro G., Massimino M., Van Meir E.G., Osuka S., Shofuda T., Klekner A., Zollo M., Leonard J.R., Rubin J.B., Jabado N., Albrecht S., Mora J., Van Meter T.E., Jung S., Moore A.S., Hallahan A.R., Chan J.A., Tirapelli D.P.C., Carlotti C.G., Fouladi M., Pimentel J., Faria C.C., Saad A.G., Massimi L., Liau L.M., Wheeler H., Nakamura H., Elbabaa S.K., Perezpena-Diazconti M., Chico Ponce de Leon F., Robinson S., Zapotocky M., Lassaletta A., Huang A., Hawkins C.E., Tabori U., Bouffet E., Bartels U., Dirks P.B., Rutka J.T., Bader G.D., Reimand J., Goldenberg A., Ramaswamy V., and Taylor M.D.

Subjects
0301 basic medicine, Cancer Research, medulloblastoma, CURRENT CONSENSUS, copy number, Bioinformatics, subgroups, Cohort Studies, Individual data, Cluster Analysis, R PACKAGE, Precision Medicine, GENECHIP DATA, Sonic hedgehog, ADULT MEDULLOBLASTOMA, DNA Copy Number Variation, Cancer, Pediatric, Genomics, methylation, CANCER, 3. Good health, Oncology, DNA methylation, Human, Pediatric Research Initiative, DNA Copy Number Variations, Pediatric Cancer, Oncology and Carcinogenesis, Computational biology, Biology, Article, CLASSIFICATION, Homogeneous clusters, 03 medical and health sciences, Rare Diseases, Genetics, medicine, Humans, Oncology & Carcinogenesis, Cerebellar Neoplasms, RECURRENCE, neoplasms, Medulloblastoma, Cluster Analysi, gene expression, MUTATIONS, subgroup, Gene Expression Profiling, Human Genome, Neurosciences, integrative clustering, DNA Methylation, medicine.disease, Precision medicine, MEDULOBLASTOMA, Brain Disorders, nervous system diseases, Brain Cancer, Gene expression profiling, stomatognathic diseases, 030104 developmental biology, Genomic, biology.protein, MOLECULAR SUBGROUPS, GENOMIC DATA, Cohort Studie
Abstract

While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma. Integrative analysis using SNF further delineates group 3 from group 4 medulloblastoma, which is not as readily apparent through analyses of individual data types. Two clear subtypes of infants with Sonic Hedgehog medulloblastoma with disparate outcomes and biology are identified. Medulloblastoma subtypes identified through integrative clustering have important implications for stratification of future clinical trials.

Published
2017

45. Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: A retrospective multicohort analysis

Author

Uri Tabori, Marta M. Alonso, Frank S. Lieberman, James T. Rutka, Xing Fan, Kevin Petrecca, Michael A. Grotzer, Lyndsey Emery, Jennifer A. Chan, Luca Massimi, Elizabeth Vera-Bolanos, Antonio Omuro, Richard Everson, Stewart Goldman, Sarah Leary, Alvaro Lassaletta, Sofia Nunes, Ralph P. Ermoian, Betty Luu, Cynthia Hawkins, Amulya A. Nageswara Rao, Jeffrey R. Leonard, Maura Massimino, Teresa Tuñón, Massimo Zollo, James M. Olson, Almos Klekner, Andrey Korshunov, Ute Bartels, Tong Lin, Roger J. Packer, Matthias A. Karajannis, David W. Ellison, Christopher Dunham, David D. Eisenstat, Jaume Mora, Martin Mynarek, Erwin G. Van Meir, Roger E. McLendon, Karel Zitterbart, Corrine Gardner, Giuseppe Cinalli, Amar Gajjar, Kenneth Aldape, Karin M. Muraszko, Vijay Ramaswamy, Thomas Hielscher, Ronald L. Hamilton, Lola B. Chambless, Michael D. Prados, David T.W. Jones, Harshad Ladha, Horacio Soto, Wiesława Grajkowska, Jason E. Cain, Felice Giangaspero, Marcel Kool, Eric S. Lipp, William H. Yong, Andrew J. Grossbach, Tibor Hortobágyi, Tarek Shalaby, Helen Wheeler, Peter Hauser, Marie Lise C. van Veelen, Kristian W. Pajtler, Dorcas Fulton, Mariarita Santi, László Bognár, Jaroslav Sterba, Jing Wu, Ji Yeoun Lee, Carlos Gilberto Carlotti, Katja von Hoff, Stefan Rutkowski, Michael D. Taylor, Daniela Pretti da Cunha Tirapelli, Phillipe Metellus, Stephen C. Mack, Thomas E. Merchant, Samer K. Elbabaa, Marc Remke, Girish Dhall, Riccardo Soffietti, Eric Bouffet, Miguel A. Guzman, Khalida Wani, Charles G. Eberhart, Terri S. Armstrong, Tom Mikkelsen, Francesca R. Buttarelli, Nada Jabado, Paul G. Fisher, Juliette Hukin, Maryam Fouladi, Sama Ahsan, Sueli Mieko Oba-Shinjo, Linda M. Liau, Satoru Osuka, Sridharan Gururangan, Peter B. Dirks, Eugene Hwang, Howard Colman, H. Ian Robins, Caterina Giannini, Suely Kazue Nagahashi Marie, Frank van Landeghem, Mark R. Gilbert, Ulrich Schüller, Florence M.G. Cavalli, David Zagzag, Ian F. Pollack, Claudia C. Faria, Stefan M. Pfister, Shin Jung, Ramaswamy, V, Hielscher, T, Mack, Sc, Lassaletta, A, Lin, T, Pajtler, Kw, Jones, Dt, Luu, B, Cavalli, Fm, Aldape, K, Remke, M, Mynarek, M, Rutkowski, S, Gururangan, S, Mclendon, Re, Lipp, E, Dunham, C, Hukin, J, Eisenstat, Dd, Fulton, D, van Landeghem, Fk, Santi, M, van Veelen, Ml, Van Meir, Eg, Osuka, S, Fan, X, Muraszko, Km, Tirapelli, Dp, Oba Shinjo, Sm, Marie, Sk, Carlotti, Cg, Lee, Jy, Rao, Aa, Giannini, C, Faria, Cc, Nunes, S, Mora, J, Hamilton, Rl, Hauser, P, Jabado, N, Petrecca, K, Jung, S, Massimi, L, Zollo, Massimo, Cinalli, G, Bognár, L, Klekner, A, Hortobágyi, T, Leary, S, Ermoian, Rp, Olson, Jm, Leonard, Jr, Gardner, C, Grajkowska, Wa, Chambless, Lb, Cain, J, Eberhart, Cg, Ahsan, S, Massimino, M, Giangaspero, F, Buttarelli, Fr, Packer, Rj, Emery, L, Yong, Wh, Soto, H, Liau, Lm, Everson, R, Grossbach, A, Shalaby, T, Grotzer, M, Karajannis, Ma, Zagzag, D, Wheeler, H, von Hoff, K, Alonso, Mm, Tuñon, T, Schüller, U, Zitterbart, K, Sterba, J, Chan, Ja, Guzman, M, Elbabaa, Sk, Colman, H, Dhall, G, Fisher, Pg, Fouladi, M, Gajjar, A, Goldman, S, Hwang, E, Kool, M, Ladha, H, Vera Bolanos, E, Wani, K, Lieberman, F, Mikkelsen, T, Omuro, Am, Pollack, If, Prados, M, Robins, Hi, Soffietti, R, Wu, J, Metellus, P, Tabori, U, Bartels, U, Bouffet, E, Hawkins, Ce, Rutka, Jt, Dirks, P, Pfister, Sm, Merchant, Te, Gilbert, Mr, Armstrong, T, Korshunov, A, Ellison, Dw, Taylor, M. d., Ramaswamy V., Hielscher T., Mack S.C., Lassaletta A., Lin T., Pajtler K.W., Jones D.T.W., Luu B., Cavalli F.M.G., Aldape K., Remke M., Mynarek M., Rutkowski S., Gururangan S., McLendon R.E., Lipp E.S., Dunham C., Hukin J., Eisenstat D.D., Fulton D., Van Landeghem F.K.H., Santi M., Van Veelen M.-L.C., Van Meir E.G., Osuka S., Fan X., Muraszko K.M., Tirapelli D.P.C., Oba-Shinjo S.M., Marie S.K.N., Carlotti C.G., Lee J.Y., Rao A.A.N., Giannini C., Faria C.C., Nunes S., Mora J., Hamilton R.L., Hauser P., Jabado N., Petrecca K., Jung S., Massimi L., Zollo M., Cinalli G., Bognar L., Klekner A., Hortobagyi T., Leary S., Ermoian R.P., Olson J.M., Leonard J.R., Gardner C., Grajkowska W.A., Chambless L.B., Cain J., Eberhart C.G., Ahsan S., Massimino M., Giangaspero F., Buttarelli F.R., Packer R.J., Emery L., Yong W.H., Soto H., Liau L.M., Everson R., Grossbach A., Shalaby T., Grotzer M., Karajannis M.A., Zagzag D., Wheeler H., Von Hoff K., Alonso M.M., Tunon T., Schuller U., Zitterbart K., Sterba J., Chan J.A., Guzman M., Elbabaa S.K., Colman H., Dhall G., Fisher P.G., Fouladi M., Gajjar A., Goldman S., Hwang E., Kool M., Ladha H., Vera-Bolanos E., Wani K., Lieberman F., Mikkelsen T., Omuro A.M., Pollack I.F., Prados M., Robins H.I., Soffietti R., Wu J., Metellus P., Tabori U., Bartels U., Bouffet E., Hawkins C.E., Rutka J.T., Dirks P., Pfister S.M., Merchant T.E., Gilbert M.R., Armstrong T.S., Korshunov A., Ellison D.W., Taylor M.D., and Neurosurgery

Subjects
Male, Ependymoma, Cancer Research, medicine.medical_treatment, cancer research, oncology, posterior fossa ependymoma, cytoreductive surgery, radiation therapy, Infratentorial Neoplasms, Cohort Studies, 0302 clinical medicine, Retrospective Studie, Medicine, Pediatric ependymoma, Child, 10. No inequality, Infratentorial Neoplasm, biology, Cytoreduction Surgical Procedures, Combined Modality Therapy, 3. Good health, Oncology, Child, Preschool, 030220 oncology & carcinogenesis, Female, Radiology, Human, Adult, medicine.medical_specialty, Adolescent, Fossa, Ependymoma, biomarkers, 03 medical and health sciences, Original Reports, Humans, Retrospective Studies, Chemotherapy, business.industry, Proportional hazards model, Infant, Retrospective cohort study, biology.organism_classification, medicine.disease, Surgery, Radiation therapy, Cohort Studie, business, 030217 neurology & neurosurgery
Abstract

Purpose Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known. Methods Four independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses. Results Molecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation. Conclusion The most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence.

Published
2016

46. Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas

Author

Elisabeth J. Rushing, Bruce Crooks, Scott L. Coven, Uri Tabori, Eric Bouffet, Claire Li, Christopher Li, Josef Zamecnik, Ute Bartels, Cynthia Hawkins, P. Daniel McNeely, Inmaculada de Prada, Michael Brudno, Michael D. Taylor, Bev Wilson, Claudia C. Faria, Livia Garzia, Vijay Ramaswamy, Lenka Krskova, Christopher Dunham, Roberto Silva, Andres Morales La Madrid, Sylvia Cheng, Ofelia Cruz, Arun K. Ramani, Michael A. Grotzer, Donna L. Johnston, Jonathan L. Finlay, David Sumerauer, Maria Joao Gil-da-Costa, Scott Ryall, Ana Guerreiro Stucklin, Yvonne Zhong, Pasqualino De Antonellis, Anthony Arnoldo, Daniel R. Boue, Koichi Ichimura, Miguel Garcia Ariza, Jean Michaud, Marta Perez-Somarriba, Motoo Nagane, Frank van Landeghem, Kohei Fukuoka, Hiroaki Sakamoto, Paul E. Kowalski, Meredith S. Irwin, Michal Zapotocky, Taylor Bridge, Iris Fried, Liana Nobre, Monique Johnson, Jordan R. Hansford, Robert Siddaway, Mary Shago, Nataliya Zhukova, Byungjin Kim, Palma Solano, Yoshiko Nakano, Keita Terashima, Alvaro Lassaletta, Angelica Oviedo, Amulya NageswaraRao, Repositório da Universidade de Lisboa, Guerreiro Stucklin, A. S., Ryall, S., Fukuoka, K., Zapotocky, M., Lassaletta, A., Li, C., Bridge, T., Kim, B., Arnoldo, A., Kowalski, P. E., Zhong, Y., Johnson, M., Ramani, A. K., Siddaway, R., Nobre, L. F., de Antonellis, P., Dunham, C., Cheng, S., Boue, D. R., Finlay, J. L., Coven, S. L., de Prada, I., Perez-Somarriba, M., Faria, C. C., Grotzer, M. A., Rushing, E., Sumerauer, D., Zamecnik, J., Krskova, L., Garcia Ariza, M., Cruz, O., Morales La Madrid, A., Solano, P., Terashima, K., Nakano, Y., Ichimura, K., Nagane, M., Sakamoto, H., Gil-da-Costa, M. J., Silva, R., Johnston, D. L., Michaud, J., Wilson, B., van Landeghem, F. K. H., Oviedo, A., Mcneely, P. D., Crooks, B., Fried, I., Zhukova, N., Hansford, J. R., Nageswararao, A., Garzia, L., Shago, M., Brudno, M., Irwin, M. S., Bartels, U., Ramaswamy, V., Bouffet, E., Taylor, M. D., Tabori, U., and Hawkins, C.

Subjects
MAPK/ERK pathway, Oncology, Epigenomics, Male, General Physics and Astronomy, Whole Exome Sequencing, Receptor tyrosine kinase, 0302 clinical medicine, Protein-Tyrosine Kinase, Cancer genomics, Anaplastic lymphoma kinase, Anaplastic Lymphoma Kinase, lcsh:Science, Exome sequencing, Proto-Oncogene Protein, Multidisciplinary, Molecular medicine, biology, Brain Neoplasms, Glioma, Protein-Tyrosine Kinases, Proto-Oncogene Proteins c-met, Receptor Protein-Tyrosine Kinase, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Female, Survival Analysi, Human, medicine.medical_specialty, Epigenomic, Science, Article, General Biochemistry, Genetics and Molecular Biology, Brain Neoplasm, 03 medical and health sciences, Internal medicine, Proto-Oncogene Proteins, Exome Sequencing, medicine, ROS1, Humans, Receptor, trkA, Survival analysis, business.industry, Infant, Newborn, Infant, Receptor Protein-Tyrosine Kinases, General Chemistry, DNA Methylation, medicine.disease, Survival Analysis, biology.protein, lcsh:Q, business, 030217 neurology & neurosurgery
Abstract

© The Author(s) 2019. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/., Infant gliomas have paradoxical clinical behavior compared to those in children and adults: low-grade tumors have a higher mortality rate, while high-grade tumors have a better outcome. However, we have little understanding of their biology and therefore cannot explain this behavior nor what constitutes optimal clinical management. Here we report a comprehensive genetic analysis of an international cohort of clinically annotated infant gliomas, revealing 3 clinical subgroups. Group 1 tumors arise in the cerebral hemispheres and harbor alterations in the receptor tyrosine kinases ALK, ROS1, NTRK and MET. These are typically single-events and confer an intermediate outcome. Groups 2 and 3 gliomas harbor RAS/MAPK pathway mutations and arise in the hemispheres and midline, respectively. Group 2 tumors have excellent long-term survival, while group 3 tumors progress rapidly and do not respond well to chemoradiation. We conclude that infant gliomas comprise 3 subgroups, justifying the need for specialized therapeutic strategies.

Published
2019

47. Subgroup and subtype‑specifc outcomes in adult medulloblastoma

Author

Konstantin Okonechnikov, Charles G. Eberhart, Roger E. McLendon, Ian F. Pollack, Stefan M. Pfister, Kyle S. Smith, Shin Jung, Noriyuki Kijima, Alexandre Vasiljevic, Karisa C. Schreck, Oksana Absalyamova, Paul A. Northcott, Daniela Pretti da Cunha Tirapelli, Rajeev Vibhakar, Sarah Leary, Olga Zheludkova, Kay K.W. Li, Lakshmikirupa Sundaresan, Seung-Ki Kim, Hallie Coltin, Jaume Mora, Erwin G. Van Meir, Wiesława Grajkowska, Marcel Kool, Daniel W. Fults, Pim J. French, Caterina Giannini, Andreas von Deimling, Jennifer A. Chan, Andrey Golanov, Linda M. Liau, Scott Raskin, Michael D. Taylor, Joshua B. Rubin, Cécile Faure-Conter, Roger J. Packer, Luca Massimi, William A. Weiss, Peter Hauser, Andrey Korshunov, Lola B. Chambless, Patryk Skowron, Carlos Gilberto Carlotti, Vijay Ramaswamy, Marie Lise C. van Veelen, Marina Ryzhova, Damian Stichel, Nalin Gupta, Johan M. Kros, Coltin H., Sundaresan L., Smith K.S., Skowron P., Massimi L., Eberhart C.G., Schreck K.C., Gupta N., Weiss W.A., Tirapelli D., Carlotti C., Li K.K.W., Ryzhova M., Golanov A., Zheludkova O., Absalyamova O., Okonechnikov K., Stichel D., von Deimling A., Giannini C., Raskin S., Van Meir E.G., Chan J.A., Fults D., Chambless L.B., Kim S.-K., Vasiljevic A., Faure-Conter C., Vibhakar R., Jung S., Leary S., Mora J., McLendon R.E., Pollack I.F., Hauser P., Grajkowska W.A., Rubin J.B., van Veelen M.-L.C., French P.J., Kros J.M., Liau L.M., Pfister S.M., Kool M., Kijima N., Taylor M.D., Packer R.J., Northcott P.A., Korshunov A., Ramaswamy V., Neurosurgery, Neurology, and Pathology

Subjects
Male, Oncology, Adult, medicine.medical_specialty, Adult Medulloblastoma, Adolescent, medicine.medical_treatment, DNA methylation profiling, Pathology and Forensic Medicine, Cohort Studies, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Risk Factors, GLI2, Internal medicine, Biomarkers, Tumor, medicine, Humans, Medulloblastoma, Sonic hedgehog, Cerebellar Neoplasms, Risk stratification, Chemotherapy, biology, business.industry, Molecular groups, medicine.disease, Molecular group, NEOPLASIAS CEREBRAIS, Progression-Free Survival, 3. Good health, Radiation therapy, PTCH1, 030220 oncology & carcinogenesis, Cohort, biology.protein, Female, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Medulloblastoma, a common pediatric malignant central nervous system tumour, represent a small proportion of brain tumours in adults. Previously it has been shown that in adults, Sonic Hedgehog (SHH)-activated tumours predominate, with Wingless-type (WNT) and Group 4 being less common, but molecular risk stratification remains a challenge. We performed an integrated analysis consisting of genome-wide methylation profiling, copy number profiling, somatic nucleotide variants and correlation of clinical variables across a cohort of 191 adult medulloblastoma cases identified through the Medulloblastoma Advanced Genomics International Consortium. We identified 30 WNT, 112 SHH, 6 Group 3, and 41 Group 4 tumours. Patients with SHH tumours were significantly older at diagnosis compared to other subgroups (p < 0.0001). Five-year progression-free survival (PFS) for WNT, SHH, Group 3, and Group 4 tumours was 64.4 (48.0-86.5), 61.9% (51.6-74.2), 80.0% (95% CI 51.6-100.0), and 44.9% (95% CI 28.6-70.7), respectively (p = 0.06). None of the clinical variables (age, sex, metastatic status, extent of resection, chemotherapy, radiotherapy) were associated with subgroup-specific PFS. Survival among patients with SHH tumours was significantly worse for cases with chromosome 3p loss (HR 2.9, 95% CI 1.1-7.6; p = 0.02), chromosome 10q loss (HR 4.6, 95% CI 2.3-9.4; p < 0.0001), chromosome 17p loss (HR 2.3, 95% CI 1.1-4.8; p = 0.02), and PTCH1 mutations (HR 2.6, 95% CI 1.1-6.2; p = 0.04). The prognostic significance of 3p loss and 10q loss persisted in multivariable regression models. For Group 4 tumours, chromosome 8 loss was strongly associated with improved survival, which was validated in a non-overlapping cohort (combined cohort HR 0.2, 95% CI 0.1-0.7; p = 0.007). Unlike in pediatric medulloblastoma, whole chromosome 11 loss in Group 4 and chromosome 14q loss in SHH was not associated with improved survival, where MYCN, GLI2 and MYC amplification were rare. In sum, we report unique subgroup-specific cytogenetic features of adult medulloblastoma, which are distinct from those in younger patients, and correlate with survival disparities. Our findings suggest that clinical trials that incorporate new strategies tailored to high-risk adult medulloblastoma patients are urgently needed.

Published
2021

48. Metabolic Regulation of the Epigenome Drives Lethal Infantile Ependymoma

Author

Samuel Weiss, Leo J.Y. Kim, Xiaochong Wu, Randy Van Ommeren, Yanqing Jiang, Kaitlin Kharas, Evgeny Kanshin, Moloud Ahmadi, Alberto Delaidelli, Geneviève Deblois, David Przelicki, Stephane Angers, Hiromichi Suzuki, Sameer Agnihotri, Bradly G. Wouters, Graham MacLeod, Ricky Tsai, Pasqualino De Antonellis, Michelle Ly, Stacey L. Krumholtz, Paul Guilhamon, James Loukides, Ravi N. Vellanki, Alex Rasnitsyn, Hamza Farooq, Daniel Schramek, Nada Jabado, María Sánchez-Osuna, Laura K. Donovan, Vijay Ramaswamy, Ibrahim El-Hamamy, Joonas Haapasalo, Jeremy N. Rich, Michael D. Taylor, Benjamin A. Garcia, Mike Tyers, Kyle Juraschka, Winnie Ong, Olivier Saulnier, Panagiotis Prinos, John J.Y. Lee, Borja L. Holgado, Olga Sirbu, Craig Daniels, Cheryl H. Arrowsmith, Cory Richman, Poul H. Sorensen, Kulandaimanuvel Antony Michealraj, Sheila K. Singh, Andrea Bajic, Polina Balin, Stephen C. Mack, Betty Luu, Fiona J. Coutinho, Dilakshan Srikanthan, Florence M.G. Cavalli, Sachin Kumar, Evan Y. Wang, Mathieu Lupien, Peter B. Dirks, Maria C. Vladoiu, Lincoln Stein, Livia Garzia, Ahmad Malik, John Wojcik, Avesta Rastan, Michealraj, K. A., Kumar, S. A., Kim, L. J. Y., Cavalli, F. M. G., Przelicki, D., Wojcik, J. B., Delaidelli, A., Bajic, A., Saulnier, O., Macleod, G., Vellanki, R. N., Vladoiu, M. C., Guilhamon, P., Ong, W., Lee, J. J. Y., Jiang, Y., Holgado, B. L., Rasnitsyn, A., Malik, A. A., Tsai, R., Richman, C. M., Juraschka, K., Haapasalo, J., Wang, E. Y., De Antonellis, P., Suzuki, H., Farooq, H., Balin, P., Kharas, K., Van Ommeren, R., Sirbu, O., Rastan, A., Krumholtz, S. L., Ly, M., Ahmadi, M., Deblois, G., Srikanthan, D., Luu, B., Loukides, J., Wu, X., Garzia, L., Ramaswamy, V., Kanshin, E., Sanchez-Osuna, M., El-Hamamy, I., Coutinho, F. J., Prinos, P., Singh, S., Donovan, L. K., Daniels, C., Schramek, D., Tyers, M., Weiss, S., Stein, L. D., Lupien, M., Wouters, B. G., Garcia, B. A., Arrowsmith, C. H., Sorensen, P. H., Angers, S., Jabado, N., Dirks, P. B., Mack, S. C., Agnihotri, S., Rich, J. N., and Taylor, M. D.

Subjects
Epigenomics, Ependymoma, Male, ependymoma, Epigenomic, Somatic cell, cancer metabolism, Infratentorial Neoplasms, Biology, General Biochemistry, Genetics and Molecular Biology, Cell Line, Histones, Brain Neoplasm, 03 medical and health sciences, Epigenome, 0302 clinical medicine, Histone demethylation, Histone methylation, medicine, Animals, Humans, Epigenetics, 030304 developmental biology, hindbrain development, Cell Proliferation, Infratentorial Neoplasm, 0303 health sciences, Brain Neoplasms, Animal, Lysine, Infant, DNA Methylation, medicine.disease, microenvironment, Mice, Inbred C57BL, Histone, Acetylation, paediatric cancer, Mutation, biology.protein, Cancer research, 030217 neurology & neurosurgery, epigenetic, Human
Abstract

Posterior fossa A (PFA) ependymomas are lethal malignancies of the hindbrain in infants and toddlers. Lacking highly recurrent somatic mutations, PFA ependymomas are proposed to be epigenetically driven tumors for which model systems are lacking. Here we demonstrate that PFA ependymomas are maintained under hypoxia, associated with restricted availability of specific metabolites to diminish histone methylation, and increase histone demethylation and acetylation at histone 3 lysine 27 (H3K27). PFA ependymomas initiate from a cell lineage in the first trimester of human development that resides in restricted oxygen. Unlike other ependymomas, transient exposure of PFA cells to ambient oxygen induces irreversible cellular toxicity. PFA tumors exhibit a low basal level of H3K27me3, and, paradoxically, inhibition of H3K27 methylation specifically disrupts PFA tumor growth. Targeting metabolism and/or the epigenome presents a unique opportunity for rational therapy for infants with PFA ependymoma. Hypoxia reprograms the cellular metabolome and epigenome to promote growth of the most lethal ependymomas.

Published
2020

49. Locoregional delivery of CAR T cells to the cerebrospinal fluid for treatment of metastatic medulloblastoma and ependymoma

Author

Carolina Nor, Martin Komosa, Olga Sirbu, Nabil Ahmed, Joonas Haapasalo, Kristen Fousek, Jonelle G. Pallota, Betty Luu, Cynthia Hawkins, Kenneth Aldape, Uri Tabori, David Przelicki, Srinidhi Varadharajan, Liam D. Hendrikse, Meenakshi Hegde, Claudia M. Kuzan-Fischer, Ana Guerreiro Stucklin, Tajana Douglas, Ahmed Z. Gad, Xiaochong Wu, Randy Van Ommeren, Polina Balin, Alex Manno, Sachin Kumar, Raul Suarez, Avesta Rastan, Craig Daniels, Mads Daugaard, Maria C. Vladoiu, Stephen Yip, Cory Richman, Michelle Ly, Matthew L. Baker, Kaitlin Kharas, Laura K. Donovan, Stephen C. Mack, Claudia C. Faria, Pasqualino De Antonellis, Ning Huang, Poul H. Sorensen, Zied Abdullaev, Lei Qin, Livia Garzia, Alyssa C. M. Joynt, A. Sorana Morrissy, Michael D. Taylor, Sujith K. Joseph, Antony Michealraj, Dilakshan Srikanthan, Florence M.G. Cavalli, Borja L. Holgado, John M. Maris, Alberto Delaidelli, Vijay Ramaswamy, Kevin Bielamowicz, Juliette Hukin, Donovan, L. K., Delaidelli, A., Joseph, S. K., Bielamowicz, K., Fousek, K., Holgado, B. L., Manno, A., Srikanthan, D., Gad, A. Z., Van Ommeren, R., Przelicki, D., Richman, C., Ramaswamy, V., Daniels, C., Pallota, J. G., Douglas, T., Joynt, A. C. M., Haapasalo, J., Nor, C., Vladoiu, M. C., Kuzan-Fischer, C. M., Garzia, L., Mack, S. C., Varadharajan, S., Baker, M. L., Hendrikse, L., Ly, M., Kharas, K., Balin, P., Wu, X., Qin, L., Huang, N., Stucklin, A. G., Morrissy, A. S., Cavalli, F. M. G., Luu, B., Suarez, R., De Antonellis, P., Michealraj, A., Rastan, A., Hegde, M., Komosa, M., Sirbu, O., Kumar, S. A., Abdullaev, Z., Faria, C. C., Yip, S., Hukin, J., Tabori, U., Hawkins, C., Aldape, K., Daugaard, M., Maris, J. M., Sorensen, P. H., Ahmed, N., and Taylor, M. D.

Subjects
0301 basic medicine, Ependymoma, Male, medicine.medical_treatment, T-Lymphocytes, Immunotherapy, Adoptive, Mice, 0302 clinical medicine, Cerebrospinal fluid, Drug Delivery Systems, HEK293 Cell, Cancer immunotherapy, Tumor Cells, Cultured, Neoplasm Metastasis, Child, Cerebrospinal Fluid, Receptors, Chimeric Antigen, Brain Neoplasms, General Medicine, Neoplasm Metastasi, Treatment Outcome, 030220 oncology & carcinogenesis, Child, Preschool, Female, Cancer Vaccine, Human, Cancer Vaccines, General Biochemistry, Genetics and Molecular Biology, Brain Neoplasm, 03 medical and health sciences, medicine, Animals, Humans, Cerebellar Neoplasms, neoplasms, Injections, Intraventricular, Medulloblastoma, Animal, business.industry, Cerebellar Neoplasm, Infant, Immunotherapy, Recurrent Medulloblastoma, medicine.disease, Interleukin-13 receptor, Xenograft Model Antitumor Assays, Chimeric antigen receptor, 030104 developmental biology, HEK293 Cells, T-Lymphocyte, Cancer research, business, Drug Delivery System
Abstract

Recurrent medulloblastoma and ependymoma are universally lethal, with no approved targeted therapies and few candidates presently under clinical evaluation. Nearly all recurrent medulloblastomas and posterior fossa group A (PFA) ependymomas are located adjacent to and bathed by the cerebrospinal fluid, presenting an opportunity for locoregional therapy, bypassing the blood–brain barrier. We identify three cell-surface targets, EPHA2, HER2 and interleukin 13 receptor α2, expressed on medulloblastomas and ependymomas, but not expressed in the normal developing brain. We validate intrathecal delivery of EPHA2, HER2 and interleukin 13 receptor α2 chimeric antigen receptor T cells as an effective treatment for primary, metastatic and recurrent group 3 medulloblastoma and PFA ependymoma xenografts in mouse models. Finally, we demonstrate that administration of these chimeric antigen receptor T cells into the cerebrospinal fluid, alone or in combination with azacytidine, is a highly effective therapy for multiple metastatic mouse models of group 3 medulloblastoma and PFA ependymoma, thereby providing a rationale for clinical trials of these approaches in humans.

Published
2019

50. A Hematogenous Route for Medulloblastoma Leptomeningeal Metastases

Author

Jennifer A. Chan, Clinton S. Robbins, Borja L. Holgado, David Shih, Maura Massimino, Vijay Ramaswamy, Jessica Liu, Robert J. Wechsler-Reya, Steven J.M. Jones, John Peacock, Michael D. Taylor, Pasqualino De Antonellis, Betty Luu, Cynthia Hawkins, Hamza Farooq, Uri Tabori, William A. Weiss, Priscilla K. Brastianos, Alex Manno, Marco A. Marra, Yuan Yao Thompson, Claudia M. Kuzan-Fischer, Kenneth Aldape, Patryk Skowron, Michal Zapotocky, Yussanne Ma, A. Sorana Morrissy, David Sumerauer, Richard D. Moore, Kory Zayne, Livia Garzia, Siddhartha Mitra, Xin Wang, Eric Bouffet, Nada Jabado, James R. Woodgett, Andrew J. Mungall, Angela Li, Kun Wei Liu, Sheila Mansouri, Peter B. Dirks, Yoon Jae Cho, Ana Guerreiro-Stucklin, Myron I. Cybulsky, Carolina Nor, Noriyuki Kijima, Michael J. Parsons, Laura K. Donovan, Poul H. Sorensen, Xiaochong Wu, Lei Qin, Sherine Ensan, Daniel W. Fults, Alexandra Garancher, Garzia, L., Kijima, N., Morrissy, A. S., De Antonellis, P., Guerreiro-Stucklin, A., Holgado, B. L., Wu, X., Wang, X., Parsons, M., Zayne, K., Manno, A., Kuzan-Fischer, C., Nor, C., Donovan, L. K., Liu, J., Qin, L., Garancher, A., Liu, K. -W., Mansouri, S., Luu, B., Thompson, Y. Y., Ramaswamy, V., Peacock, J., Farooq, H., Skowron, P., Shih, D. J. H., Li, A., Ensan, S., Robbins, C. S., Cybulsky, M., Mitra, S., Ma, Y., Moore, R., Mungall, A., Cho, Y. -J., Weiss, W. A., Chan, J. A., Hawkins, C. E., Massimino, M., Jabado, N., Zapotocky, M., Sumerauer, D., Bouffet, E., Dirks, P., Tabori, U., Sorensen, P. H. B., Brastianos, P. K., Aldape, K., Jones, S. J. M., Marra, M. A., Woodgett, J. R., Wechsler-Reya, R. J., Fults, D. W., and Taylor, M. D.

Subjects
0301 basic medicine, Male, Pathology, Cell, Mice, SCID, Neoplastic Cells, Medical and Health Sciences, Mice, 0302 clinical medicine, Circulating tumor cell, Cerebrospinal fluid, Allograft, Meningeal Neoplasms, Circulating, Pair 10, Meningeal Neoplasm, Chemokine CCL2, Cancer, Pediatric, Tumor, Leptomeninges, Biological Sciences, Allografts, Neoplastic Cells, Circulating, Primary tumor, 3. Good health, pediatric cancer, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, brain tumor, Human, medicine.medical_specialty, Parabiosis, Pediatric Cancer, Biology, circulating tumor cells, SCID, medulloblastoma, circulating tumor cell, General Biochemistry, Genetics and Molecular Biology, Chromosomes, Article, Cell Line, 03 medical and health sciences, Rare Diseases, Cell Line, Tumor, medicine, Animals, Humans, metastases, neoplasms, Medulloblastoma, Animal, Chromosomes, Human, Pair 10, Neurosciences, medicine.disease, Spinal cord, Pediatric cancer, Brain Disorders, nervous system diseases, Brain Cancer, stomatognathic diseases, 030104 developmental biology, metastase, Cancer research, brain tumors, 030217 neurology & neurosurgery, Developmental Biology
Abstract

While the preponderance of morbidity and mortality in medulloblastoma patients are due to metastatic disease, most research focuses on the primary tumor due to a dearth of metastatic tissue samples and model systems. Medulloblastoma metastases are found almost exclusively on the leptomeningeal surface of the brain and spinal cord; dissemination is therefore thought to occur through shedding of primary tumor cells into the cerebrospinal fluid followed by distal re-implantation on the leptomeninges. We present evidence for medulloblastoma circulating tumor cells (CTCs) in therapy-naive patients and demonstrate in vivo, through flank xenografting and parabiosis, that medulloblastoma CTCs can spread through the blood to the leptomeningeal space to form leptomeningeal metastases. Medulloblastoma leptomeningeal metastases express high levels of the chemokine CCL2, and expression of CCL2 in medulloblastoma in vivo is sufficient to drive leptomeningeal dissemination. Hematogenous dissemination of medulloblastoma offers a new opportunity to diagnose and treat lethal disseminated medulloblastoma. In addition to disseminating through the cerebrospinal fluid, medulloblastoma can metastasize through circulating tumor cells in the blood, thereby providing a different angle for clinical diagnosis and treatment development.

Published
2018

Catalog

Books, media, physical & digital resources
See catalog results