Search

Your search keyword '"Van Meter T"' showing total 4 results
Start Over Author "Van Meter T" Topic epigenesis, genetic
4 results on '"Van Meter T"'

1. Epigenomic alterations define lethal CIMP-positive ependymomas of infancy.

Author

Mack SC, Witt H, Piro RM, Gu L, Zuyderduyn S, Stütz AM, Wang X, Gallo M, Garzia L, Zayne K, Zhang X, Ramaswamy V, Jäger N, Jones DT, Sill M, Pugh TJ, Ryzhova M, Wani KM, Shih DJ, Head R, Remke M, Bailey SD, Zichner T, Faria CC, Barszczyk M, Stark S, Seker-Cin H, Hutter S, Johann P, Bender S, Hovestadt V, Tzaridis T, Dubuc AM, Northcott PA, Peacock J, Bertrand KC, Agnihotri S, Cavalli FM, Clarke I, Nethery-Brokx K, Creasy CL, Verma SK, Koster J, Wu X, Yao Y, Milde T, Sin-Chan P, Zuccaro J, Lau L, Pereira S, Castelo-Branco P, Hirst M, Marra MA, Roberts SS, Fults D, Massimi L, Cho YJ, Van Meter T, Grajkowska W, Lach B, Kulozik AE, von Deimling A, Witt O, Scherer SW, Fan X, Muraszko KM, Kool M, Pomeroy SL, Gupta N, Phillips J, Huang A, Tabori U, Hawkins C, Malkin D, Kongkham PN, Weiss WA, Jabado N, Rutka JT, Bouffet E, Korbel JO, Lupien M, Aldape KD, Bader GD, Eils R, Lichter P, Dirks PB, Pfister SM, Korshunov A, and Taylor MD

Subjects
Animals, Brain Neoplasms drug therapy, Brain Neoplasms genetics, DNA Methylation drug effects, Embryonic Stem Cells metabolism, Ependymoma drug therapy, Epigenomics, Female, Gene Expression Regulation, Neoplastic, Gene Silencing drug effects, Histones drug effects, Histones metabolism, Humans, Infant, Mice, Mice, Inbred NOD, Mice, SCID, Mutation genetics, Phenotype, Polycomb Repressive Complex 2 metabolism, Prognosis, Rhombencephalon pathology, Xenograft Model Antitumor Assays, CpG Islands genetics, Ependymoma genetics, Epigenesis, Genetic genetics
Abstract

Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not further increase survival. Whole-genome and whole-exome sequencing of 47 hindbrain ependymomas reveals an extremely low mutation rate, and zero significant recurrent somatic single nucleotide variants. Although devoid of recurrent single nucleotide variants and focal copy number aberrations, poor-prognosis hindbrain ependymomas exhibit a CpG island methylator phenotype. Transcriptional silencing driven by CpG methylation converges exclusively on targets of the Polycomb repressive complex 2 which represses expression of differentiation genes through trimethylation of H3K27. CpG island methylator phenotype-positive hindbrain ependymomas are responsive to clinical drugs that target either DNA or H3K27 methylation both in vitro and in vivo. We conclude that epigenetic modifiers are the first rational therapeutic candidates for this deadly malignancy, which is epigenetically deregulated but genetically bland.

Published
2014
Full Text
View/download PDF

2. Hotspot mutations in H3F3A and IDH1 define distinct epigenetic and biological subgroups of glioblastoma.

Author

Sturm D, Witt H, Hovestadt V, Khuong-Quang DA, Jones DT, Konermann C, Pfaff E, Tönjes M, Sill M, Bender S, Kool M, Zapatka M, Becker N, Zucknick M, Hielscher T, Liu XY, Fontebasso AM, Ryzhova M, Albrecht S, Jacob K, Wolter M, Ebinger M, Schuhmann MU, van Meter T, Frühwald MC, Hauch H, Pekrun A, Radlwimmer B, Niehues T, von Komorowski G, Dürken M, Kulozik AE, Madden J, Donson A, Foreman NK, Drissi R, Fouladi M, Scheurlen W, von Deimling A, Monoranu C, Roggendorf W, Herold-Mende C, Unterberg A, Kramm CM, Felsberg J, Hartmann C, Wiestler B, Wick W, Milde T, Witt O, Lindroth AM, Schwartzentruber J, Faury D, Fleming A, Zakrzewska M, Liberski PP, Zakrzewski K, Hauser P, Garami M, Klekner A, Bognar L, Morrissy S, Cavalli F, Taylor MD, van Sluis P, Koster J, Versteeg R, Volckmann R, Mikkelsen T, Aldape K, Reifenberger G, Collins VP, Majewski J, Korshunov A, Lichter P, Plass C, Jabado N, and Pfister SM

Subjects
Adult, Brain Neoplasms pathology, Child, DNA Methylation, Glioblastoma pathology, Humans, Receptor, Platelet-Derived Growth Factor alpha genetics, Transcriptome, Brain Neoplasms genetics, Epigenesis, Genetic, Glioblastoma genetics, Histones genetics, Isocitrate Dehydrogenase genetics, Mutation
Abstract

Glioblastoma (GBM) is a brain tumor that carries a dismal prognosis and displays considerable heterogeneity. We have recently identified recurrent H3F3A mutations affecting two critical amino acids (K27 and G34) of histone H3.3 in one-third of pediatric GBM. Here, we show that each H3F3A mutation defines an epigenetic subgroup of GBM with a distinct global methylation pattern, and that they are mutually exclusive with IDH1 mutations, which characterize a third mutation-defined subgroup. Three further epigenetic subgroups were enriched for hallmark genetic events of adult GBM and/or established transcriptomic signatures. We also demonstrate that the two H3F3A mutations give rise to GBMs in separate anatomic compartments, with differential regulation of transcription factors OLIG1, OLIG2, and FOXG1, possibly reflecting different cellular origins., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Published
2012
Full Text
View/download PDF

3. Genetic and epigenetic inactivation of Kruppel-like factor 4 in medulloblastoma.

Author

Nakahara Y, Northcott PA, Li M, Kongkham PN, Smith C, Yan H, Croul S, Ra YS, Eberhart C, Huang A, Bigner D, Grajkowska W, Van Meter T, Rutka JT, and Taylor MD

Subjects
Adult, Animals, Antimetabolites, Antineoplastic pharmacology, Azacitidine pharmacology, Cell Line, Tumor, Cerebellar Neoplasms pathology, CpG Islands genetics, DNA Methylation drug effects, Gene Expression Regulation, Neoplastic drug effects, Gene Expression Regulation, Neoplastic genetics, Humans, Kaplan-Meier Estimate, Kruppel-Like Factor 4, Loss of Heterozygosity, Medulloblastoma pathology, Mice, Mice, Nude, Neoplasms, Experimental genetics, Neoplasms, Experimental pathology, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Promoter Regions, Genetic genetics, Reverse Transcriptase Polymerase Chain Reaction, Transplantation, Heterologous, Cerebellar Neoplasms genetics, Epigenesis, Genetic, Kruppel-Like Transcription Factors genetics, Medulloblastoma genetics
Abstract

Although medulloblastoma is the most common pediatric malignant brain tumor, its molecular underpinnings are largely unknown. We have identified rare, recurrent homozygous deletions of Kruppel-like Factor 4 (KLF4) in medulloblastoma using high-resolution single nucleotide polymorphism arrays, digital karyotyping, and genomic real-time polymerase chain reaction (PCR). Furthermore, we show that there is loss of physiological KLF4 expression in more than 40% of primary medulloblastomas both at the RNA and protein levels. Medulloblastoma cell lines drastically increase the expression of KLF4 in response to the demethylating agent 5-azacytidine and demonstrate dense methylation of the promoter CpG island by bisulfite sequencing. Methylation-specific PCR targeting the KLF4 promoter demonstrates CpG methylation in approximately 16% of primary medulloblastomas. Reexpression of KLF4 in the D283 medulloblastoma cell line results in significant growth suppression both in vitro and in vivo. We conclude that KLF4 is inactivated by either genetic or epigenetic mechanisms in a large subset of medulloblastomas and that it likely functions as a tumor suppressor gene in the pathogenesis of medulloblastoma.

Published
2010
Full Text
View/download PDF

4. Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors

Author

Constanze Zeller, Joseph D. Norman, Man Yu, Jian Qiang Lu, Doug Strother, Miklós Garami, C. Jane McGlade, Seung-Ki Kim, Misko Dzamba, Ronald Grant, David D. Eisenstat, Beverly Wilson, Anat Erdreich-Epstein, Almos Klekner, A. Sorana Morrissy, Richard Grundy, Young Shin Ra, Joanna J. Phillips, Alexandre Montpetit, Takafumi Wataya, Alexander R. Judkins, Shayna Zelcer, Nicholas K. Foreman, Rishi Lulla, Aline Cristiane Planello, Marc Remke, Harriet Druker, Annie Huang, Torsten Pietsch, José Pimentel, Jordan R. Hansford, Lindsey M. Hoffman, Mark Barszczyk, Tarik Tihan, Eugene Hwang, Vivek Mehta, László Bognár, Louis Letourneau, Donna L. Johnston, Stephen Yip, Lucie Lafay-Cousin, Mei Lu, Pasqualino De Antonellis, Katrin Scheinemann, Deena M.A. Gendoo, Shengrui Feng, James T. Rutka, G. Yancey Gillespie, Ho Keung Ng, Robert Hammond, David Malkin, Lúcia Roque, Anne Sophie Carret, King Ching Ho, Helen Toledano, Jennifer A. Chan, Monika Warmuth-Metz, Jacek Majewski, Jonathon Torchia, Livia Garzia, Stefan Rutkowski, Gino R. Somers, Tibor Hortobágyi, Ute Bartels, Peter Hauser, Ulrich Schüller, Cynthia Hawkins, Shih Hwa Chiou, Eric Bouffet, Adam Fleming, Alexandra N. Riemenschneider, Timothy E. Van Meter, Vijay Ramaswamy, Hideo Nakamura, Tiago Medina, Alexandre Vasiljevic, Noppadol Larbcharoensub, Patrick Sin-Chan, Christopher Dunham, Theodore Nicolaides, Iris Fried, Daniel Picard, Maryam Fouladi, Chris Fryer, Brian Golbourn, Mathieu Bourgey, Jean Michaud, Claudia C. Faria, Gary D. Bader, Mathieu Lupien, Amar Gajjar, Guillaume Bourque, Peter B. Dirks, Steffen Albrecht, Suradej Hongeng, Cheryl H. Arrowsmith, Uri Tabori, David A. Ramsay, Dalia Barsyte-Lovejoy, Paul Guilhamon, Michael Brudno, Nada Jabado, Juliette Hukin, Dong Anh Khuong-Quang, Michael D. Taylor, Tiffany Chan, Natalia R. Agamez, Daniel D. De Carvalho, Nongnuch Sirachainan, Samina Afzal, Seung Ah Choi, Diane K. Birks, Daniel W. Fults, Andrew S. Moore, Alyssa Reddy, Jason Fangusaro, Daniel Catchpoole, Yin Wang, Torchia, J., Golbourn, B., Feng, S., Ho, K. C., Sin-Chan, P., Vasiljevic, A., Norman, J. D., Guilhamon, P., Garzia, L., Agamez, N. R., Lu, M., Chan, T. S., Picard, D., de Antonellis, P., Khuong-Quang, D. -A., Planello, A. C., Zeller, C., Barsyte-Lovejoy, D., Lafay-Cousin, L., Letourneau, L., Bourgey, M., Yu, M., Gendoo, D. M. A., Dzamba, M., Barszczyk, M., Medina, T., Riemenschneider, A. N., Morrissy, A. S., Ra, Y. -S., Ramaswamy, V., Remke, M., Dunham, C. P., Yip, S., Ng, H. -K., Lu, J. -Q., Mehta, V., Albrecht, S., Pimentel, J., Chan, J. A., Somers, G. R., Faria, C. C., Roque, L., Fouladi, M., Hoffman, L. M., Moore, A. S., Wang, Y., Choi, S. A., Hansford, J. R., Catchpoole, D., Birks, D. K., Foreman, N. K., Strother, D., Klekner, A., Bognar, L., Garami, M., Hauser, P., Hortobagyi, T., Wilson, B., Hukin, J., Carret, A. -S., Van Meter, T. E., Hwang, E. I., Gajjar, A., Chiou, S. -H., Nakamura, H., Toledano, H., Fried, I., Fults, D., Wataya, T., Fryer, C., Eisenstat, D. D., Scheinemann, K., Fleming, A. J., Johnston, D. L., Michaud, J., Zelcer, S., Hammond, R., Afzal, S., Ramsay, D. A., Sirachainan, N., Hongeng, S., Larbcharoensub, N., Grundy, R. G., Lulla, R. R., Fangusaro, J. R., Druker, H., Bartels, U., Grant, R., Malkin, D., Mcglade, C. J., Nicolaides, T., Tihan, T., Phillips, J., Majewski, J., Montpetit, A., Bourque, G., Bader, G. D., Reddy, A. T., Gillespie, G. Y., Warmuth-Metz, M., Rutkowski, S., Tabori, U., Lupien, M., Brudno, M., Schuller, U., Pietsch, T., Judkins, A. R., Hawkins, C. E., Bouffet, E., Kim, S. -K., Dirks, P. B., Taylor, M. D., Erdreich-Epstein, A., Arrowsmith, C. H., De Carvalho, D. D., Rutka, J. T., Jabado, N., and Huang, A.

Subjects
Epigenomics, 0301 basic medicine, Cancer Research, Dasatinib, 1109 Neurosciences, 1112 Oncology and Carcinogenesis, ATRT, Epigenesis, Genetic, Central Nervous System Neoplasms, genomic, SMARCB1, Epigenesis, Central Nervous System Neoplasm, Teratoma, SMARCB1 Protein, Orvostudományok, Chromatin, 3. Good health, Oncology, DNA methylation, subgroup-specific therapeutic, Human, medicine.drug, Epigenomic, Cell Survival, Protein Kinase Inhibitor, Biology, Klinikai orvostudományok, Article, Receptor, Platelet-Derived Growth Factor beta, 03 medical and health sciences, Cell Line, Tumor, medicine, Humans, Oncology & Carcinogenesis, Epigenetics, Protein Kinase Inhibitors, rhabdoid tumor, Rhabdoid Tumor, Cell Proliferation, Cancer, DNA Methylation, medicine.disease, Pyrimidines, 030104 developmental biology, Pyrimidine, Mutation, Cancer research, enhancer
Abstract

We recently reported that atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In this study, we analyzed 191 primary ATRTs and 10 ATRT cell lines to define the genomic and epigenomic landscape of ATRTs and identify subgroup-specific therapeutic targets. We found ATRTs segregated into three epigenetic subgroups with distinct genomic profiles, SMARCB1 genotypes, and chromatin landscape that correlated with differential cellular responses to a panel of signaling and epigenetic inhibitors. Significantly, we discovered that differential methylation of a PDGFRB-associated enhancer confers specific sensitivity of group 2 ATRT cells to dasatinib and nilotinib, and suggest that these are promising therapies for this highly lethal ATRT subtype.

Published
2016

Catalog

Books, media, physical & digital resources
See catalog results