Search

Your search keyword '"Andrey Korshunov"' showing total 540 results
Start Over Author "Andrey Korshunov" Database OpenAIRE
540 results on '"Andrey Korshunov"'

1. Comparison of transcriptome profiles between medulloblastoma primary and recurrent tumors uncovers novel variance effects in relapses

Author

Konstantin Okonechnikov, Aniello Federico, Daniel Schrimpf, Philipp Sievers, Felix Sahm, Jan Koster, David T. W. Jones, Andreas von Deimling, Stefan M. Pfister, Marcel Kool, Andrey Korshunov, Center of Experimental and Molecular Medicine, AII - Cancer immunology, and CCA - Cancer biology and immunology

Subjects
Cellular and Molecular Neuroscience, Neurology (clinical), Prognosis, Transcriptomics, Pathology and Forensic Medicine, Medulloblastoma, Relapses
Abstract

Nowadays medulloblastoma (MB) tumors can be treated with risk-stratified approaches with up to 80% success rate. However, disease relapses occur in approximately 30% of patients and successful salvage treatment strategies at relapse remain scarce. Acquired copy number changes or TP53 mutations are known to occur frequently in relapses, while methylation profiles usually remain highly similar to those of the matching primary tumors, indicating that in general molecular subgrouping does not change during the course of the disease. In the current study, we have used RNA sequencing data to analyze the transcriptome profiles of 43 primary-relapse MB pairs in order to identify specific molecular features of relapses within various tumor groups. Gene variance analysis between primary and relapse samples demonstrated the impact of age in SHH-MB: the changes in gene expression relapse profiles were more pronounced in the younger patients (

Published
2023

2. Correction to: Amplification of the PLAG-family genes—PLAGL1 and PLAGL2—is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification

Author

Michaela-Kristina Keck, Martin Sill, Andrea Wittmann, Piyush Joshi, Damian Stichel, Pengbo Beck, Konstantin Okonechnikow, Philipp Sievers, Annika K. Wefers, Federico Roncaroli, Shivaram Avula, Martin G. McCabe, James T. Hayden, Pieter Wesseling, Ingrid Øra, Monica Nistér, Mariëtte E. G. Kranendonk, Bastiaan B. J. Tops, Michal Zapotocky, Josef Zamecnik, Alexandre Vasiljevic, Tanguy Fenouil, David Meyronet, Katja von Hoff, Ulrich Schüller, Hugues Loiseau, Dominique Figarella-Branger, Christof M. Kramm, Dominik Sturm, David Scheie, Tuomas Rauramaa, Jouni Pesola, Johannes Gojo, Christine Haberler, Sebastian Brandner, Tom Jacques, Alexandra Sexton Oates, Richard Saffery, Ewa Koscielniak, Suzanne J. Baker, Stephen Yip, Matija Snuderl, Nasir Ud Din, David Samuel, Kathrin Schramm, Mirjam Blattner-Johnson, Florian Selt, Jonas Ecker, Till Milde, Andreas von Deimling, Andrey Korshunov, Arie Perry, Stefan M. Pfister, Felix Sahm, David A. Solomon, and David T. W. Jones

Subjects
Cellular and Molecular Neuroscience, Neurology (clinical), Pathology and Forensic Medicine
Published
2023

3. Clinical outcome following surgical resection and radiotherapy in adult patients with pleomorphic xanthoastrocytoma as defined by DNA methylation profiling

Author

Maximilian Deng, Felix Hinz, Semi Harrabi, Dominik Sturm, Martin Sill, Andrey Korshunov, Tanja Eichkorn, Juliane Hörner-Rieber, Klaus Herfarth, Christine Jungk, Andreas Unterberg, Stefan Pfister, Wolfgang Wick, Andreas von Deimling, David Jones, Jürgen Debus, Felix Sahm, and Laila König

Subjects
Medicine (miscellaneous)
Abstract

Background Molecular brain tumor classification using DNA methylation profiling has revealed that the methylation-class of pleomorphic xanthoastrocytoma (mcPXA) comprised a substantial portion of divergent initial diagnoses, which had been established based on histology alone. This study aimed to characterize the survival outcome in patients with mcPXAs—in light of the diverse selected treatment regimes. Methods A retrospective cohort of adult mcPXAs were analyzed in regard to their progression-free survival following surgical resection and postoperative radiotherapy. Radiotherapy treatment plans were correlated with follow-up images to characterize the pattern of relapse. Treatment toxicities and molecular tumor characteristics were further analyzed. Results Divergent initial histological diagnoses were encountered in 40.7%. There was no significant difference in local progression-free (PFS) and overall survival (OS) following gross total or subtotal resection. Postoperative radiotherapy was completed in 81% (22/27) following surgical intervention. Local PFS was 54.4% (95% CI: 35.3–84.0%) and OS was 81.3% (95% CI: 63.8–100%) after 3 years following postoperative radiotherapy. Initial relapses post-radiotherapy were primarily located in the previous tumor location and/or the planning target volume (PTV) (12/13). All patients in our cohort demonstrated the prognostically favorable pTERT-wildtype mcPXA. Conclusion Our study demonstrated that adult patients with mcPXAs display a worse progression-free survival compared to the reported WHO grade 2 PXAs. Future matched-pair analyses are required with a non-irradiated cohort to elucidate the benefit of postoperative radiotherapy in adult patients with mcPXAs.

Published
2023

4. Epigenetic profiling reveals a subset of pediatric-type glioneuronal tumors characterized by oncogenic gene fusions involving several targetable kinases

Author

Philipp Sievers, Martin Sill, Daniel Schrimpf, Dennis Friedel, Dominik Sturm, Maria Gardberg, Kathreena M. Kurian, Lenka Krskova, Ales Vicha, Tina Schaller, Christian Hagel, Zied Abdullaev, Kenneth Aldape, Thomas S. Jacques, Andrey Korshunov, Wolfgang Wick, Stefan M. Pfister, Andreas von Deimling, David T. W. Jones, and Felix Sahm

Subjects
Cellular and Molecular Neuroscience, Humans, Oncogene Fusion, ddc:610, Neurology (clinical), Gene Fusion, Child, Neoplasms, Neuroepithelial, Epigenesis, Genetic, Pathology and Forensic Medicine
Published
2022

5. The first-in-class ERK inhibitor ulixertinib shows promising activity in mitogen-activated protein kinase (MAPK)-driven pediatric low-grade glioma models

Author

Romain Sigaud, Lisa Rösch, Charlotte Gatzweiler, Julia Benzel, Laura von Soosten, Heike Peterziel, Florian Selt, Sara Najafi, Simay Ayhan, Xenia F Gerloff, Nina Hofmann, Isabel Büdenbender, Lukas Schmitt, Kathrin I Foerster, Jürgen Burhenne, Walter E Haefeli, Andrey Korshunov, Felix Sahm, Cornelis M van Tilburg, David T W Jones, Stefan M Pfister, Deborah Knoerzer, Brent L Kreider, Max Sauter, Kristian W Pajtler, Marc Zuckermann, Ina Oehme, Olaf Witt, and Till Milde

Subjects
Cancer Research, Oncology, Neurology (clinical)
Abstract

Background Pediatric low-grade gliomas (pLGG) are the most common pediatric central nervous system tumors, with driving alterations typically occurring in the MAPK pathway. The ERK1/2 inhibitor ulixertinib (BVD-523) has shown promising responses in adult patients with mitogen-activated protein kinase (MAPK)-driven solid tumors. Methods We investigated the antitumoral activity of ulixertinib monotherapy as well as in combination with MEK inhibitors (MEKi), BH3-mimetics, or chemotherapy in pLGG. Patient-derived pLGG models reflecting the two most common alterations in the disease, KIAA1549:BRAF-fusion and BRAFV600E mutation (DKFZ-BT66 and BT40, respectively) were used for in vitro and in vivo (zebrafish embryos and mice) efficacy testing. Results Ulixertinib inhibited MAPK pathway activity in both models, and reduced cell viability in BT40 with clinically achievable concentrations in the low nanomolar range. Combination treatment of ulixertinib with MEKi or BH3-mimetics showed strong evidence of antiproliferative synergy in vitro. Ulixertinib showed on-target activity in all tested combinations. In vivo, sufficient penetrance of the drug into brain tumor tissue in concentrations above the in vitro IC50 and reduction of MAPK pathway activity was achieved. In a preclinical mouse trial, ulixertinib mono- and combined therapies slowed tumor growth and increased survival. Conclusions These data indicate a high clinical potential of ulixertinib for the treatment of pLGG and strongly support its first clinical evaluation in pLGG as single agent and in combination therapy in a currently planned international phase I/II umbrella trial.

Published
2022

6. Transcriptome analysis stratifies second-generation non-WNT/non-SHH medulloblastoma subgroups into clinically tractable subtypes

Author

Andrey Korshunov, Konstantin Okonechnikov, Daniel Schrimpf, Svenja Tonn, Martin Mynarek, Jan Koster, Philipp Sievers, Till Milde, Felix Sahm, David T. W. Jones, Andreas von Deimling, Stefan M. Pfister, Marcel Kool, Center of Experimental and Molecular Medicine, AII - Cancer immunology, and CCA - Cancer biology and immunology

Subjects
Cellular and Molecular Neuroscience, Non-WNT/non-SHH, Transcriptomic, Subgroups, Neurology (clinical), Prognosis, Pathology and Forensic Medicine, Medulloblastoma
Abstract

Medulloblastoma (MB), one of the most common malignant pediatric brain tumor, is a heterogenous disease comprised of four distinct molecular groups (WNT, SHH, Group 3, Group 4). Each of these groups can be further subdivided into second-generation MB (SGS MB) molecular subgroups, each with distinct genetic and clinical characteristics. For instance, non-WNT/non-SHH MB (Group 3/4) can be subdivided molecularly into eight distinct and clinically relevant tumor subgroups. A further molecular stratification/summarization of these SGS MB would allow for the assignment of patients to risk-associated treatment protocols. Here, we performed DNA- and RNA-based analysis of 574 non-WNT/non-SHH MB and analyzed the clinical significance of various molecular patterns within the entire cohort and the eight SGS MB, with the aim to develop an optimal risk stratification of these tumors. Multigene analysis disclosed several survival-associated genes highly specific for each molecular subgroup within this non-WNT/non-SHH MB cohort with minimal inter-subgroup overlap. These subgroup-specific and prognostically relevant genes were associated with pathways that could underlie SGS MB clinical-molecular diversity and tumor-driving mechanisms. By combining survival-associated genes within each SGS MB, distinct metagene sets being appropriate for their optimal risk stratification were identified. Defined subgroup-specific metagene sets were independent variables in the multivariate models generated for each SGS MB and their prognostic value was confirmed in a completely non-overlapping validation cohort of non-WNT/non-SHH MB (n = 377). In summary, the current results indicate that the integration of transcriptome data in risk stratification models may improve outcome prediction for each non-WNT/non-SHH SGS MB. Identified subgroup-specific gene expression signatures could be relevant for clinical implementation and survival-associated metagene sets could be adopted for further SGS MB risk stratification. Future studies should aim at validating the prognostic role of these transcriptome-based SGS MB subtypes in prospective clinical trials.

Published
2023

7. HIP1R and vimentin immunohistochemistry predict 1p/19q status in IDH-mutant glioma

Author

Marius Felix, Dennis Friedel, Ashok Kumar Jayavelu, Katharina Filipski, Annekathrin Reinhardt, Uwe Warnken, Damian Stichel, Daniel Schrimpf, Andrey Korshunov, Yueting Wang, Tobias Kessler, Nima Etminan, Andreas Unterberg, Christel Herold-Mende, Laura Heikaus, Felix Sahm, Wolfgang Wick, Patrick N Harter, Andreas von Deimling, and David E Reuss

Subjects
Proteomics, Cancer Research, Brain Neoplasms, Oligodendroglioma, Microfilament Proteins, Glioma, Astrocytoma, Immunohistochemistry, Isocitrate Dehydrogenase, Oncology, Chromosomes, Human, Pair 1, Mutation, Basic and Translational Investigations, Humans, Vimentin, Neurology (clinical), Chromosomes, Human, Pair 19, Adaptor Proteins, Signal Transducing
Abstract

Background IDH-mutant gliomas are separate based on the codeletion of the chromosomal arms 1p and 19q into oligodendrogliomas IDH-mutant 1p/19q-codeleted and astrocytomas IDH-mutant. While nuclear loss of ATRX expression excludes 1p/19q codeletion, its limited sensitivity prohibits to conclude on 1p/19q status in tumors with retained nuclear ATRX expression. Methods Employing mass spectrometry based proteomic analysis in a discovery series containing 35 fresh frozen and 72 formalin fixed and paraffin embedded tumors with established IDH and 1p/19q status, potential biomarkers were discovered. Subsequent validation immunohistochemistry was conducted on two independent series (together 77 oligodendrogliomas IDH-mutant 1p/19q-codeleted and 92 astrocytomas IDH-mutant). Results We detected highly specific protein patterns distinguishing oligodendroglioma and astrocytoma. In these patterns, high HIP1R and low vimentin levels were observed in oligodendroglioma while low HIP1R and high vimentin levels occurred in astrocytoma. Immunohistochemistry for HIP1R and vimentin expression in 35 cases from the FFPE discovery series confirmed these findings. Blinded evaluation of the validation cohorts predicted the 1p/19q status with a positive and negative predictive value as well as an accuracy of 100% in the first cohort and with a positive predictive value of 83%; negative predictive value of 100% and an accuracy of 92% in the second cohort. Nuclear ATRX loss as marker for astrocytoma increased the sensitivity to 96% and the specificity to 100%. Conclusions We demonstrate that immunohistochemistry for HIP1R, vimentin, and ATRX predict 1p/19q status with 100% specificity and 95% sensitivity and therefore, constitutes a simple and inexpensive approach to the classification of IDH-mutant glioma.

Published
2023

8. Supplementary Table S1 from Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes

Author

Chris Jones, David T.W. Jones, Thomas S. Jacques, David W. Ellison, Sergey Popov, David Capper, Maria Vinci, Andrea Carai, Angela Mastronuzzi, Suzanne J. Baker, Felix Sahm, Stefan M. Pfister, Christof M. Kramm, Andreas von Deimling, Lynley V. Marshall, Fernando Carceller, Darren R. Hargrave, Kristian Aquilina, Matthias A. Karajannis, David S. Ziegler, Mark J. Cowley, Maria Tsoli, Stephen P. Lowis, Timothy E.G. Hassall, Andrew S. Moore, Simon Bailey, Francesca Diomedi-Camassei, Giovanna Stefania Colafati, Evelina Miele, Clare Mitchell, Tabitha Bloom, Olaf Witt, Marc Zuckermann, Dominik Sturm, Barbara C. Worst, Lotte Hiddingh, Andrey Korshunov, Pablo Hernáiz Driever, Felipe Andreiuolo, Torsten Pietsch, Simone Hettmer, Kornelius Kerl, Winand N.M. Dinjens, Martin Ebinger, Martin U. Schuhmann, Jens Schittenhelm, Michael Karremann, Michael Capra, Jane B. Cryan, Michael Farrell, Petter Brandal, Thale Kristin Olsen, David A. Solomon, Monika Ashok Davare, Lissa Baird, Matthew D. Wood, Barbara Faganel Kotnik, Mara Popović, Shani Caspi, Ho-Keung Ng, Roger Packer, Irene Slavc, Christine Haberler, Matthias Preusser, Tobey J. Macdonald, Paula Z. Proszek, Debbie Hughes, Marc K. Rosenblum, Stephen W. Gilheeney, Ira J. Dunkel, Martin Sill, Simon P. Robinson, Jessica K.R. Boult, Rachael Natrajan, Claire Cairns, Bassel Zebian, Christopher Chandler, Safa Al-Sarraj, Lawrence J. Doey, Andrew J. Martin, Leslie Bridges, Matija Snuderl, David E. Kram, Uwe Kordes, Ulrich Schüller, Jeffrey Knipstein, Stephen Crosier, Mellissa Maybury, Catherine Rowe, Kathreena M. Kurian, Michael Hubank, Ji Wen, Wilda Orisme, James D. Dalton, Kelly Haupfear, Mark Kristiansen, Jane Chalker, Aimee Avery, Amy R. Fairchild, Alex Virasami, Louise Howell, Anna Burford, Valeria Molinari, Diana M. Carvalho, Sara Temelso, Elisa Izquierdo, Iris Stoler, Tejus A. Bale, Scott Newman, Ruth G. Tatevossian, Jessica C. Pickles, Britta Ismer, Alan Mackay, and Matthew Clarke

Abstract

Supplementary Table S1

Published
2023

9. Supplementary Table S1 from Cross-Species Genomics Reveals Oncogenic Dependencies in ZFTA/C11orf95 Fusion–Positive Supratentorial Ependymomas

Author

Kristian W. Pajtler, Daisuke Kawauchi, Felix Sahm, Stefan M. Pfister, Andreas von Deimling, Marcel Kool, David T.W. Jones, Richard J. Gilbertson, Stephen C. Mack, Mikio Hoshino, Richard G. Grundy, Till Milde, Matija Snuderl, Johan M. Kros, Pablo Hernáiz Driever, Sebastian Brandner, Ulrich Schüller, Christel C. Herold-Mende, David W. Ellison, David Capper, Vijay Ramaswamy, Andrew M. Donson, Stefan Rutkowski, Gudrun Fleischhack, Guido Reifenberger, Dominique Figarella-Branger, Christine Haberler, Rebecca Chapman, Florian Selt, Philipp Sievers, Jonas Ecker, Dominik Sturm, Nicolas U. Gerber, Ryo Shiraishi, Toma Adachi, Shinichiro Taya, Julia Benzel, Robert Kupp, Amir Arabzade, Damian Stichel, Johannes Gojo, Marina Ryzhova, Patricia Benites Goncalves da Silva, Kendra K. Maass, Martin Sill, Andrey Korshunov, Konstantin Okonechnikov, David R. Ghasemi, and Tuyu Zheng

Abstract

Suppl. Table S1 - A summary of the human cohort used for DNA methylation-profiling_DRG3003

Published
2023

10. Supplementary Table S3 from Cross-Species Genomics Reveals Oncogenic Dependencies in ZFTA/C11orf95 Fusion–Positive Supratentorial Ependymomas

Author

Kristian W. Pajtler, Daisuke Kawauchi, Felix Sahm, Stefan M. Pfister, Andreas von Deimling, Marcel Kool, David T.W. Jones, Richard J. Gilbertson, Stephen C. Mack, Mikio Hoshino, Richard G. Grundy, Till Milde, Matija Snuderl, Johan M. Kros, Pablo Hernáiz Driever, Sebastian Brandner, Ulrich Schüller, Christel C. Herold-Mende, David W. Ellison, David Capper, Vijay Ramaswamy, Andrew M. Donson, Stefan Rutkowski, Gudrun Fleischhack, Guido Reifenberger, Dominique Figarella-Branger, Christine Haberler, Rebecca Chapman, Florian Selt, Philipp Sievers, Jonas Ecker, Dominik Sturm, Nicolas U. Gerber, Ryo Shiraishi, Toma Adachi, Shinichiro Taya, Julia Benzel, Robert Kupp, Amir Arabzade, Damian Stichel, Johannes Gojo, Marina Ryzhova, Patricia Benites Goncalves da Silva, Kendra K. Maass, Martin Sill, Andrey Korshunov, Konstantin Okonechnikov, David R. Ghasemi, and Tuyu Zheng

Abstract

Suppl. Table S3 - Differentially expressed genes of ST-EPN-RELA and cluster 2 - 4

Published
2023

11. Supplementary Table S2 from Cross-Species Genomics Reveals Oncogenic Dependencies in ZFTA/C11orf95 Fusion–Positive Supratentorial Ependymomas

Author

Kristian W. Pajtler, Daisuke Kawauchi, Felix Sahm, Stefan M. Pfister, Andreas von Deimling, Marcel Kool, David T.W. Jones, Richard J. Gilbertson, Stephen C. Mack, Mikio Hoshino, Richard G. Grundy, Till Milde, Matija Snuderl, Johan M. Kros, Pablo Hernáiz Driever, Sebastian Brandner, Ulrich Schüller, Christel C. Herold-Mende, David W. Ellison, David Capper, Vijay Ramaswamy, Andrew M. Donson, Stefan Rutkowski, Gudrun Fleischhack, Guido Reifenberger, Dominique Figarella-Branger, Christine Haberler, Rebecca Chapman, Florian Selt, Philipp Sievers, Jonas Ecker, Dominik Sturm, Nicolas U. Gerber, Ryo Shiraishi, Toma Adachi, Shinichiro Taya, Julia Benzel, Robert Kupp, Amir Arabzade, Damian Stichel, Johannes Gojo, Marina Ryzhova, Patricia Benites Goncalves da Silva, Kendra K. Maass, Martin Sill, Andrey Korshunov, Konstantin Okonechnikov, David R. Ghasemi, and Tuyu Zheng

Abstract

Suppl. Table S2 - Copy number alterations for all 613 tumors

Published
2023

12. Supplementary Data from Cross-Species Genomics Reveals Oncogenic Dependencies in ZFTA/C11orf95 Fusion–Positive Supratentorial Ependymomas

Author

Kristian W. Pajtler, Daisuke Kawauchi, Felix Sahm, Stefan M. Pfister, Andreas von Deimling, Marcel Kool, David T.W. Jones, Richard J. Gilbertson, Stephen C. Mack, Mikio Hoshino, Richard G. Grundy, Till Milde, Matija Snuderl, Johan M. Kros, Pablo Hernáiz Driever, Sebastian Brandner, Ulrich Schüller, Christel C. Herold-Mende, David W. Ellison, David Capper, Vijay Ramaswamy, Andrew M. Donson, Stefan Rutkowski, Gudrun Fleischhack, Guido Reifenberger, Dominique Figarella-Branger, Christine Haberler, Rebecca Chapman, Florian Selt, Philipp Sievers, Jonas Ecker, Dominik Sturm, Nicolas U. Gerber, Ryo Shiraishi, Toma Adachi, Shinichiro Taya, Julia Benzel, Robert Kupp, Amir Arabzade, Damian Stichel, Johannes Gojo, Marina Ryzhova, Patricia Benites Goncalves da Silva, Kendra K. Maass, Martin Sill, Andrey Korshunov, Konstantin Okonechnikov, David R. Ghasemi, and Tuyu Zheng

Abstract

Supplementary Figures and methods

Published
2023

13. Supplementary Data from Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes

Author

Chris Jones, David T.W. Jones, Thomas S. Jacques, David W. Ellison, Sergey Popov, David Capper, Maria Vinci, Andrea Carai, Angela Mastronuzzi, Suzanne J. Baker, Felix Sahm, Stefan M. Pfister, Christof M. Kramm, Andreas von Deimling, Lynley V. Marshall, Fernando Carceller, Darren R. Hargrave, Kristian Aquilina, Matthias A. Karajannis, David S. Ziegler, Mark J. Cowley, Maria Tsoli, Stephen P. Lowis, Timothy E.G. Hassall, Andrew S. Moore, Simon Bailey, Francesca Diomedi-Camassei, Giovanna Stefania Colafati, Evelina Miele, Clare Mitchell, Tabitha Bloom, Olaf Witt, Marc Zuckermann, Dominik Sturm, Barbara C. Worst, Lotte Hiddingh, Andrey Korshunov, Pablo Hernáiz Driever, Felipe Andreiuolo, Torsten Pietsch, Simone Hettmer, Kornelius Kerl, Winand N.M. Dinjens, Martin Ebinger, Martin U. Schuhmann, Jens Schittenhelm, Michael Karremann, Michael Capra, Jane B. Cryan, Michael Farrell, Petter Brandal, Thale Kristin Olsen, David A. Solomon, Monika Ashok Davare, Lissa Baird, Matthew D. Wood, Barbara Faganel Kotnik, Mara Popović, Shani Caspi, Ho-Keung Ng, Roger Packer, Irene Slavc, Christine Haberler, Matthias Preusser, Tobey J. Macdonald, Paula Z. Proszek, Debbie Hughes, Marc K. Rosenblum, Stephen W. Gilheeney, Ira J. Dunkel, Martin Sill, Simon P. Robinson, Jessica K.R. Boult, Rachael Natrajan, Claire Cairns, Bassel Zebian, Christopher Chandler, Safa Al-Sarraj, Lawrence J. Doey, Andrew J. Martin, Leslie Bridges, Matija Snuderl, David E. Kram, Uwe Kordes, Ulrich Schüller, Jeffrey Knipstein, Stephen Crosier, Mellissa Maybury, Catherine Rowe, Kathreena M. Kurian, Michael Hubank, Ji Wen, Wilda Orisme, James D. Dalton, Kelly Haupfear, Mark Kristiansen, Jane Chalker, Aimee Avery, Amy R. Fairchild, Alex Virasami, Louise Howell, Anna Burford, Valeria Molinari, Diana M. Carvalho, Sara Temelso, Elisa Izquierdo, Iris Stoler, Tejus A. Bale, Scott Newman, Ruth G. Tatevossian, Jessica C. Pickles, Britta Ismer, Alan Mackay, and Matthew Clarke

Abstract

Supplementary Figures and Legends

Published
2023

14. Table S1 from Desmoplastic Infantile Ganglioglioma/Astrocytoma (DIG/DIA) Are Distinct Entities with Frequent BRAFV600 Mutations

Author

Jeffrey G. Ojemann, Richard G. Ellenbogen, Amy Lee, Eric C. Holland, J. Russell Geyer, James M. Olson, Chibawanye Ene, Shelly Wang, Aria Fallah, Andrey Korshunov, David Capper, Lukas Chavez, Christina M. Lockwood, Sarah E.S. Leary, Bonnie L. Cole, Isaac Joshua Abecassis, David T.W. Jones, and Anthony C. Wang

Abstract

SCH Clinical and Sequencing Data

Published
2023

15. Supplementary Table S5 from Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes

Author

Chris Jones, David T.W. Jones, Thomas S. Jacques, David W. Ellison, Sergey Popov, David Capper, Maria Vinci, Andrea Carai, Angela Mastronuzzi, Suzanne J. Baker, Felix Sahm, Stefan M. Pfister, Christof M. Kramm, Andreas von Deimling, Lynley V. Marshall, Fernando Carceller, Darren R. Hargrave, Kristian Aquilina, Matthias A. Karajannis, David S. Ziegler, Mark J. Cowley, Maria Tsoli, Stephen P. Lowis, Timothy E.G. Hassall, Andrew S. Moore, Simon Bailey, Francesca Diomedi-Camassei, Giovanna Stefania Colafati, Evelina Miele, Clare Mitchell, Tabitha Bloom, Olaf Witt, Marc Zuckermann, Dominik Sturm, Barbara C. Worst, Lotte Hiddingh, Andrey Korshunov, Pablo Hernáiz Driever, Felipe Andreiuolo, Torsten Pietsch, Simone Hettmer, Kornelius Kerl, Winand N.M. Dinjens, Martin Ebinger, Martin U. Schuhmann, Jens Schittenhelm, Michael Karremann, Michael Capra, Jane B. Cryan, Michael Farrell, Petter Brandal, Thale Kristin Olsen, David A. Solomon, Monika Ashok Davare, Lissa Baird, Matthew D. Wood, Barbara Faganel Kotnik, Mara Popović, Shani Caspi, Ho-Keung Ng, Roger Packer, Irene Slavc, Christine Haberler, Matthias Preusser, Tobey J. Macdonald, Paula Z. Proszek, Debbie Hughes, Marc K. Rosenblum, Stephen W. Gilheeney, Ira J. Dunkel, Martin Sill, Simon P. Robinson, Jessica K.R. Boult, Rachael Natrajan, Claire Cairns, Bassel Zebian, Christopher Chandler, Safa Al-Sarraj, Lawrence J. Doey, Andrew J. Martin, Leslie Bridges, Matija Snuderl, David E. Kram, Uwe Kordes, Ulrich Schüller, Jeffrey Knipstein, Stephen Crosier, Mellissa Maybury, Catherine Rowe, Kathreena M. Kurian, Michael Hubank, Ji Wen, Wilda Orisme, James D. Dalton, Kelly Haupfear, Mark Kristiansen, Jane Chalker, Aimee Avery, Amy R. Fairchild, Alex Virasami, Louise Howell, Anna Burford, Valeria Molinari, Diana M. Carvalho, Sara Temelso, Elisa Izquierdo, Iris Stoler, Tejus A. Bale, Scott Newman, Ruth G. Tatevossian, Jessica C. Pickles, Britta Ismer, Alan Mackay, and Matthew Clarke

Abstract

Supplementary Table S5

Published
2023

16. Supplementary Table S6 from Cross-Species Genomics Reveals Oncogenic Dependencies in ZFTA/C11orf95 Fusion–Positive Supratentorial Ependymomas

Author

Kristian W. Pajtler, Daisuke Kawauchi, Felix Sahm, Stefan M. Pfister, Andreas von Deimling, Marcel Kool, David T.W. Jones, Richard J. Gilbertson, Stephen C. Mack, Mikio Hoshino, Richard G. Grundy, Till Milde, Matija Snuderl, Johan M. Kros, Pablo Hernáiz Driever, Sebastian Brandner, Ulrich Schüller, Christel C. Herold-Mende, David W. Ellison, David Capper, Vijay Ramaswamy, Andrew M. Donson, Stefan Rutkowski, Gudrun Fleischhack, Guido Reifenberger, Dominique Figarella-Branger, Christine Haberler, Rebecca Chapman, Florian Selt, Philipp Sievers, Jonas Ecker, Dominik Sturm, Nicolas U. Gerber, Ryo Shiraishi, Toma Adachi, Shinichiro Taya, Julia Benzel, Robert Kupp, Amir Arabzade, Damian Stichel, Johannes Gojo, Marina Ryzhova, Patricia Benites Goncalves da Silva, Kendra K. Maass, Martin Sill, Andrey Korshunov, Konstantin Okonechnikov, David R. Ghasemi, and Tuyu Zheng

Abstract

Suppl. Table S6 - Primer list

Published
2023

17. Supplementary Table S2 from Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes

Author

Chris Jones, David T.W. Jones, Thomas S. Jacques, David W. Ellison, Sergey Popov, David Capper, Maria Vinci, Andrea Carai, Angela Mastronuzzi, Suzanne J. Baker, Felix Sahm, Stefan M. Pfister, Christof M. Kramm, Andreas von Deimling, Lynley V. Marshall, Fernando Carceller, Darren R. Hargrave, Kristian Aquilina, Matthias A. Karajannis, David S. Ziegler, Mark J. Cowley, Maria Tsoli, Stephen P. Lowis, Timothy E.G. Hassall, Andrew S. Moore, Simon Bailey, Francesca Diomedi-Camassei, Giovanna Stefania Colafati, Evelina Miele, Clare Mitchell, Tabitha Bloom, Olaf Witt, Marc Zuckermann, Dominik Sturm, Barbara C. Worst, Lotte Hiddingh, Andrey Korshunov, Pablo Hernáiz Driever, Felipe Andreiuolo, Torsten Pietsch, Simone Hettmer, Kornelius Kerl, Winand N.M. Dinjens, Martin Ebinger, Martin U. Schuhmann, Jens Schittenhelm, Michael Karremann, Michael Capra, Jane B. Cryan, Michael Farrell, Petter Brandal, Thale Kristin Olsen, David A. Solomon, Monika Ashok Davare, Lissa Baird, Matthew D. Wood, Barbara Faganel Kotnik, Mara Popović, Shani Caspi, Ho-Keung Ng, Roger Packer, Irene Slavc, Christine Haberler, Matthias Preusser, Tobey J. Macdonald, Paula Z. Proszek, Debbie Hughes, Marc K. Rosenblum, Stephen W. Gilheeney, Ira J. Dunkel, Martin Sill, Simon P. Robinson, Jessica K.R. Boult, Rachael Natrajan, Claire Cairns, Bassel Zebian, Christopher Chandler, Safa Al-Sarraj, Lawrence J. Doey, Andrew J. Martin, Leslie Bridges, Matija Snuderl, David E. Kram, Uwe Kordes, Ulrich Schüller, Jeffrey Knipstein, Stephen Crosier, Mellissa Maybury, Catherine Rowe, Kathreena M. Kurian, Michael Hubank, Ji Wen, Wilda Orisme, James D. Dalton, Kelly Haupfear, Mark Kristiansen, Jane Chalker, Aimee Avery, Amy R. Fairchild, Alex Virasami, Louise Howell, Anna Burford, Valeria Molinari, Diana M. Carvalho, Sara Temelso, Elisa Izquierdo, Iris Stoler, Tejus A. Bale, Scott Newman, Ruth G. Tatevossian, Jessica C. Pickles, Britta Ismer, Alan Mackay, and Matthew Clarke

Abstract

Supplementary Table S2

Published
2023

18. Supplementary Table S4 from Cross-Species Genomics Reveals Oncogenic Dependencies in ZFTA/C11orf95 Fusion–Positive Supratentorial Ependymomas

Author

Kristian W. Pajtler, Daisuke Kawauchi, Felix Sahm, Stefan M. Pfister, Andreas von Deimling, Marcel Kool, David T.W. Jones, Richard J. Gilbertson, Stephen C. Mack, Mikio Hoshino, Richard G. Grundy, Till Milde, Matija Snuderl, Johan M. Kros, Pablo Hernáiz Driever, Sebastian Brandner, Ulrich Schüller, Christel C. Herold-Mende, David W. Ellison, David Capper, Vijay Ramaswamy, Andrew M. Donson, Stefan Rutkowski, Gudrun Fleischhack, Guido Reifenberger, Dominique Figarella-Branger, Christine Haberler, Rebecca Chapman, Florian Selt, Philipp Sievers, Jonas Ecker, Dominik Sturm, Nicolas U. Gerber, Ryo Shiraishi, Toma Adachi, Shinichiro Taya, Julia Benzel, Robert Kupp, Amir Arabzade, Damian Stichel, Johannes Gojo, Marina Ryzhova, Patricia Benites Goncalves da Silva, Kendra K. Maass, Martin Sill, Andrey Korshunov, Konstantin Okonechnikov, David R. Ghasemi, and Tuyu Zheng

Abstract

Suppl. Table S4 - Histopathological evaluation of 25 cases

Published
2023

19. Data from Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes

Author

Chris Jones, David T.W. Jones, Thomas S. Jacques, David W. Ellison, Sergey Popov, David Capper, Maria Vinci, Andrea Carai, Angela Mastronuzzi, Suzanne J. Baker, Felix Sahm, Stefan M. Pfister, Christof M. Kramm, Andreas von Deimling, Lynley V. Marshall, Fernando Carceller, Darren R. Hargrave, Kristian Aquilina, Matthias A. Karajannis, David S. Ziegler, Mark J. Cowley, Maria Tsoli, Stephen P. Lowis, Timothy E.G. Hassall, Andrew S. Moore, Simon Bailey, Francesca Diomedi-Camassei, Giovanna Stefania Colafati, Evelina Miele, Clare Mitchell, Tabitha Bloom, Olaf Witt, Marc Zuckermann, Dominik Sturm, Barbara C. Worst, Lotte Hiddingh, Andrey Korshunov, Pablo Hernáiz Driever, Felipe Andreiuolo, Torsten Pietsch, Simone Hettmer, Kornelius Kerl, Winand N.M. Dinjens, Martin Ebinger, Martin U. Schuhmann, Jens Schittenhelm, Michael Karremann, Michael Capra, Jane B. Cryan, Michael Farrell, Petter Brandal, Thale Kristin Olsen, David A. Solomon, Monika Ashok Davare, Lissa Baird, Matthew D. Wood, Barbara Faganel Kotnik, Mara Popović, Shani Caspi, Ho-Keung Ng, Roger Packer, Irene Slavc, Christine Haberler, Matthias Preusser, Tobey J. Macdonald, Paula Z. Proszek, Debbie Hughes, Marc K. Rosenblum, Stephen W. Gilheeney, Ira J. Dunkel, Martin Sill, Simon P. Robinson, Jessica K.R. Boult, Rachael Natrajan, Claire Cairns, Bassel Zebian, Christopher Chandler, Safa Al-Sarraj, Lawrence J. Doey, Andrew J. Martin, Leslie Bridges, Matija Snuderl, David E. Kram, Uwe Kordes, Ulrich Schüller, Jeffrey Knipstein, Stephen Crosier, Mellissa Maybury, Catherine Rowe, Kathreena M. Kurian, Michael Hubank, Ji Wen, Wilda Orisme, James D. Dalton, Kelly Haupfear, Mark Kristiansen, Jane Chalker, Aimee Avery, Amy R. Fairchild, Alex Virasami, Louise Howell, Anna Burford, Valeria Molinari, Diana M. Carvalho, Sara Temelso, Elisa Izquierdo, Iris Stoler, Tejus A. Bale, Scott Newman, Ruth G. Tatevossian, Jessica C. Pickles, Britta Ismer, Alan Mackay, and Matthew Clarke

Abstract

Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histologic review, methylation profiling, and custom panel, genome, or exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an “intrinsic” spectrum of disease specific to the infant population. These included those with targetable MAPK alterations, and a large proportion of remaining cases harboring gene fusions targeting ALK (n = 31), NTRK1/2/3 (n = 21), ROS1 (n = 9), and MET (n = 4) as their driving alterations, with evidence of efficacy of targeted agents in the clinic. These data strongly support the concept that infant gliomas require a change in diagnostic practice and management.Significance:Infant high-grade gliomas in the cerebral hemispheres comprise novel subgroups, with a prevalence of ALK, NTRK1/2/3, ROS1, or MET gene fusions. Kinase fusion–positive tumors have better outcome and respond to targeted therapy clinically. Other subgroups have poor outcome, with fusion-negative cases possibly representing an epigenetically driven pluripotent stem cell phenotype.See related video: https://vimeo.com/438254885See related commentary by Szulzewsky and Cimino, p. 904.This article is highlighted in the In This Issue feature, p. 890

Published
2023

20. Supplementary Table S6 from Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes

Author

Chris Jones, David T.W. Jones, Thomas S. Jacques, David W. Ellison, Sergey Popov, David Capper, Maria Vinci, Andrea Carai, Angela Mastronuzzi, Suzanne J. Baker, Felix Sahm, Stefan M. Pfister, Christof M. Kramm, Andreas von Deimling, Lynley V. Marshall, Fernando Carceller, Darren R. Hargrave, Kristian Aquilina, Matthias A. Karajannis, David S. Ziegler, Mark J. Cowley, Maria Tsoli, Stephen P. Lowis, Timothy E.G. Hassall, Andrew S. Moore, Simon Bailey, Francesca Diomedi-Camassei, Giovanna Stefania Colafati, Evelina Miele, Clare Mitchell, Tabitha Bloom, Olaf Witt, Marc Zuckermann, Dominik Sturm, Barbara C. Worst, Lotte Hiddingh, Andrey Korshunov, Pablo Hernáiz Driever, Felipe Andreiuolo, Torsten Pietsch, Simone Hettmer, Kornelius Kerl, Winand N.M. Dinjens, Martin Ebinger, Martin U. Schuhmann, Jens Schittenhelm, Michael Karremann, Michael Capra, Jane B. Cryan, Michael Farrell, Petter Brandal, Thale Kristin Olsen, David A. Solomon, Monika Ashok Davare, Lissa Baird, Matthew D. Wood, Barbara Faganel Kotnik, Mara Popović, Shani Caspi, Ho-Keung Ng, Roger Packer, Irene Slavc, Christine Haberler, Matthias Preusser, Tobey J. Macdonald, Paula Z. Proszek, Debbie Hughes, Marc K. Rosenblum, Stephen W. Gilheeney, Ira J. Dunkel, Martin Sill, Simon P. Robinson, Jessica K.R. Boult, Rachael Natrajan, Claire Cairns, Bassel Zebian, Christopher Chandler, Safa Al-Sarraj, Lawrence J. Doey, Andrew J. Martin, Leslie Bridges, Matija Snuderl, David E. Kram, Uwe Kordes, Ulrich Schüller, Jeffrey Knipstein, Stephen Crosier, Mellissa Maybury, Catherine Rowe, Kathreena M. Kurian, Michael Hubank, Ji Wen, Wilda Orisme, James D. Dalton, Kelly Haupfear, Mark Kristiansen, Jane Chalker, Aimee Avery, Amy R. Fairchild, Alex Virasami, Louise Howell, Anna Burford, Valeria Molinari, Diana M. Carvalho, Sara Temelso, Elisa Izquierdo, Iris Stoler, Tejus A. Bale, Scott Newman, Ruth G. Tatevossian, Jessica C. Pickles, Britta Ismer, Alan Mackay, and Matthew Clarke

Abstract

Supplementary Table S6

Published
2023

21. Supplementary Table S5 from Cross-Species Genomics Reveals Oncogenic Dependencies in ZFTA/C11orf95 Fusion–Positive Supratentorial Ependymomas

Author

Kristian W. Pajtler, Daisuke Kawauchi, Felix Sahm, Stefan M. Pfister, Andreas von Deimling, Marcel Kool, David T.W. Jones, Richard J. Gilbertson, Stephen C. Mack, Mikio Hoshino, Richard G. Grundy, Till Milde, Matija Snuderl, Johan M. Kros, Pablo Hernáiz Driever, Sebastian Brandner, Ulrich Schüller, Christel C. Herold-Mende, David W. Ellison, David Capper, Vijay Ramaswamy, Andrew M. Donson, Stefan Rutkowski, Gudrun Fleischhack, Guido Reifenberger, Dominique Figarella-Branger, Christine Haberler, Rebecca Chapman, Florian Selt, Philipp Sievers, Jonas Ecker, Dominik Sturm, Nicolas U. Gerber, Ryo Shiraishi, Toma Adachi, Shinichiro Taya, Julia Benzel, Robert Kupp, Amir Arabzade, Damian Stichel, Johannes Gojo, Marina Ryzhova, Patricia Benites Goncalves da Silva, Kendra K. Maass, Martin Sill, Andrey Korshunov, Konstantin Okonechnikov, David R. Ghasemi, and Tuyu Zheng

Abstract

Suppl. Table S5 - GO analysis for C11orf95-target models specific DEGs

Published
2023

22. Supplementary Table S7 from Cross-Species Genomics Reveals Oncogenic Dependencies in ZFTA/C11orf95 Fusion–Positive Supratentorial Ependymomas

Author

Kristian W. Pajtler, Daisuke Kawauchi, Felix Sahm, Stefan M. Pfister, Andreas von Deimling, Marcel Kool, David T.W. Jones, Richard J. Gilbertson, Stephen C. Mack, Mikio Hoshino, Richard G. Grundy, Till Milde, Matija Snuderl, Johan M. Kros, Pablo Hernáiz Driever, Sebastian Brandner, Ulrich Schüller, Christel C. Herold-Mende, David W. Ellison, David Capper, Vijay Ramaswamy, Andrew M. Donson, Stefan Rutkowski, Gudrun Fleischhack, Guido Reifenberger, Dominique Figarella-Branger, Christine Haberler, Rebecca Chapman, Florian Selt, Philipp Sievers, Jonas Ecker, Dominik Sturm, Nicolas U. Gerber, Ryo Shiraishi, Toma Adachi, Shinichiro Taya, Julia Benzel, Robert Kupp, Amir Arabzade, Damian Stichel, Johannes Gojo, Marina Ryzhova, Patricia Benites Goncalves da Silva, Kendra K. Maass, Martin Sill, Andrey Korshunov, Konstantin Okonechnikov, David R. Ghasemi, and Tuyu Zheng

Abstract

Suppl. Table S7 - Antibody list

Published
2023

23. Supplementary Table S7 from Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes

Author

Chris Jones, David T.W. Jones, Thomas S. Jacques, David W. Ellison, Sergey Popov, David Capper, Maria Vinci, Andrea Carai, Angela Mastronuzzi, Suzanne J. Baker, Felix Sahm, Stefan M. Pfister, Christof M. Kramm, Andreas von Deimling, Lynley V. Marshall, Fernando Carceller, Darren R. Hargrave, Kristian Aquilina, Matthias A. Karajannis, David S. Ziegler, Mark J. Cowley, Maria Tsoli, Stephen P. Lowis, Timothy E.G. Hassall, Andrew S. Moore, Simon Bailey, Francesca Diomedi-Camassei, Giovanna Stefania Colafati, Evelina Miele, Clare Mitchell, Tabitha Bloom, Olaf Witt, Marc Zuckermann, Dominik Sturm, Barbara C. Worst, Lotte Hiddingh, Andrey Korshunov, Pablo Hernáiz Driever, Felipe Andreiuolo, Torsten Pietsch, Simone Hettmer, Kornelius Kerl, Winand N.M. Dinjens, Martin Ebinger, Martin U. Schuhmann, Jens Schittenhelm, Michael Karremann, Michael Capra, Jane B. Cryan, Michael Farrell, Petter Brandal, Thale Kristin Olsen, David A. Solomon, Monika Ashok Davare, Lissa Baird, Matthew D. Wood, Barbara Faganel Kotnik, Mara Popović, Shani Caspi, Ho-Keung Ng, Roger Packer, Irene Slavc, Christine Haberler, Matthias Preusser, Tobey J. Macdonald, Paula Z. Proszek, Debbie Hughes, Marc K. Rosenblum, Stephen W. Gilheeney, Ira J. Dunkel, Martin Sill, Simon P. Robinson, Jessica K.R. Boult, Rachael Natrajan, Claire Cairns, Bassel Zebian, Christopher Chandler, Safa Al-Sarraj, Lawrence J. Doey, Andrew J. Martin, Leslie Bridges, Matija Snuderl, David E. Kram, Uwe Kordes, Ulrich Schüller, Jeffrey Knipstein, Stephen Crosier, Mellissa Maybury, Catherine Rowe, Kathreena M. Kurian, Michael Hubank, Ji Wen, Wilda Orisme, James D. Dalton, Kelly Haupfear, Mark Kristiansen, Jane Chalker, Aimee Avery, Amy R. Fairchild, Alex Virasami, Louise Howell, Anna Burford, Valeria Molinari, Diana M. Carvalho, Sara Temelso, Elisa Izquierdo, Iris Stoler, Tejus A. Bale, Scott Newman, Ruth G. Tatevossian, Jessica C. Pickles, Britta Ismer, Alan Mackay, and Matthew Clarke

Abstract

Supplementary Table S7

Published
2023

24. Supplementary Table S4 from Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes

Author

Chris Jones, David T.W. Jones, Thomas S. Jacques, David W. Ellison, Sergey Popov, David Capper, Maria Vinci, Andrea Carai, Angela Mastronuzzi, Suzanne J. Baker, Felix Sahm, Stefan M. Pfister, Christof M. Kramm, Andreas von Deimling, Lynley V. Marshall, Fernando Carceller, Darren R. Hargrave, Kristian Aquilina, Matthias A. Karajannis, David S. Ziegler, Mark J. Cowley, Maria Tsoli, Stephen P. Lowis, Timothy E.G. Hassall, Andrew S. Moore, Simon Bailey, Francesca Diomedi-Camassei, Giovanna Stefania Colafati, Evelina Miele, Clare Mitchell, Tabitha Bloom, Olaf Witt, Marc Zuckermann, Dominik Sturm, Barbara C. Worst, Lotte Hiddingh, Andrey Korshunov, Pablo Hernáiz Driever, Felipe Andreiuolo, Torsten Pietsch, Simone Hettmer, Kornelius Kerl, Winand N.M. Dinjens, Martin Ebinger, Martin U. Schuhmann, Jens Schittenhelm, Michael Karremann, Michael Capra, Jane B. Cryan, Michael Farrell, Petter Brandal, Thale Kristin Olsen, David A. Solomon, Monika Ashok Davare, Lissa Baird, Matthew D. Wood, Barbara Faganel Kotnik, Mara Popović, Shani Caspi, Ho-Keung Ng, Roger Packer, Irene Slavc, Christine Haberler, Matthias Preusser, Tobey J. Macdonald, Paula Z. Proszek, Debbie Hughes, Marc K. Rosenblum, Stephen W. Gilheeney, Ira J. Dunkel, Martin Sill, Simon P. Robinson, Jessica K.R. Boult, Rachael Natrajan, Claire Cairns, Bassel Zebian, Christopher Chandler, Safa Al-Sarraj, Lawrence J. Doey, Andrew J. Martin, Leslie Bridges, Matija Snuderl, David E. Kram, Uwe Kordes, Ulrich Schüller, Jeffrey Knipstein, Stephen Crosier, Mellissa Maybury, Catherine Rowe, Kathreena M. Kurian, Michael Hubank, Ji Wen, Wilda Orisme, James D. Dalton, Kelly Haupfear, Mark Kristiansen, Jane Chalker, Aimee Avery, Amy R. Fairchild, Alex Virasami, Louise Howell, Anna Burford, Valeria Molinari, Diana M. Carvalho, Sara Temelso, Elisa Izquierdo, Iris Stoler, Tejus A. Bale, Scott Newman, Ruth G. Tatevossian, Jessica C. Pickles, Britta Ismer, Alan Mackay, and Matthew Clarke

Abstract

Supplementary Table S4

Published
2023

25. Data from Cross-Species Genomics Reveals Oncogenic Dependencies in ZFTA/C11orf95 Fusion–Positive Supratentorial Ependymomas

Author

Kristian W. Pajtler, Daisuke Kawauchi, Felix Sahm, Stefan M. Pfister, Andreas von Deimling, Marcel Kool, David T.W. Jones, Richard J. Gilbertson, Stephen C. Mack, Mikio Hoshino, Richard G. Grundy, Till Milde, Matija Snuderl, Johan M. Kros, Pablo Hernáiz Driever, Sebastian Brandner, Ulrich Schüller, Christel C. Herold-Mende, David W. Ellison, David Capper, Vijay Ramaswamy, Andrew M. Donson, Stefan Rutkowski, Gudrun Fleischhack, Guido Reifenberger, Dominique Figarella-Branger, Christine Haberler, Rebecca Chapman, Florian Selt, Philipp Sievers, Jonas Ecker, Dominik Sturm, Nicolas U. Gerber, Ryo Shiraishi, Toma Adachi, Shinichiro Taya, Julia Benzel, Robert Kupp, Amir Arabzade, Damian Stichel, Johannes Gojo, Marina Ryzhova, Patricia Benites Goncalves da Silva, Kendra K. Maass, Martin Sill, Andrey Korshunov, Konstantin Okonechnikov, David R. Ghasemi, and Tuyu Zheng

Abstract

Molecular groups of supratentorial ependymomas comprise tumors with ZFTA–RELA or YAP1-involving fusions and fusion-negative subependymoma. However, occasionally supratentorial ependymomas cannot be readily assigned to any of these groups due to lack of detection of a typical fusion and/or ambiguous DNA methylation–based classification. An unbiased approach with a cohort of unprecedented size revealed distinct methylation clusters composed of tumors with ependymal but also various other histologic features containing alternative translocations that shared ZFTA as a partner gene. Somatic overexpression of ZFTA-associated fusion genes in the developing cerebral cortex is capable of inducing tumor formation in vivo, and cross-species comparative analyses identified GLI2 as a key downstream regulator of tumorigenesis in all tumors. Targeting GLI2 with arsenic trioxide caused extended survival of tumor-bearing animals, indicating a potential therapeutic vulnerability in ZFTA fusion–positive tumors.Significance:ZFTA–RELA fusions are a hallmark feature of supratentorial ependymoma. We find that ZFTA acts as a partner for alternative transcriptional activators in oncogenic fusions of supratentorial tumors with various histologic characteristics. Establishing representative mouse models, we identify potential therapeutic targets shared by ZFTA fusion–positive tumors, such as GLI2.This article is highlighted in the In This Issue feature, p. 2113

Published
2023

26. Supplementary Table S3 from Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes

Author

Chris Jones, David T.W. Jones, Thomas S. Jacques, David W. Ellison, Sergey Popov, David Capper, Maria Vinci, Andrea Carai, Angela Mastronuzzi, Suzanne J. Baker, Felix Sahm, Stefan M. Pfister, Christof M. Kramm, Andreas von Deimling, Lynley V. Marshall, Fernando Carceller, Darren R. Hargrave, Kristian Aquilina, Matthias A. Karajannis, David S. Ziegler, Mark J. Cowley, Maria Tsoli, Stephen P. Lowis, Timothy E.G. Hassall, Andrew S. Moore, Simon Bailey, Francesca Diomedi-Camassei, Giovanna Stefania Colafati, Evelina Miele, Clare Mitchell, Tabitha Bloom, Olaf Witt, Marc Zuckermann, Dominik Sturm, Barbara C. Worst, Lotte Hiddingh, Andrey Korshunov, Pablo Hernáiz Driever, Felipe Andreiuolo, Torsten Pietsch, Simone Hettmer, Kornelius Kerl, Winand N.M. Dinjens, Martin Ebinger, Martin U. Schuhmann, Jens Schittenhelm, Michael Karremann, Michael Capra, Jane B. Cryan, Michael Farrell, Petter Brandal, Thale Kristin Olsen, David A. Solomon, Monika Ashok Davare, Lissa Baird, Matthew D. Wood, Barbara Faganel Kotnik, Mara Popović, Shani Caspi, Ho-Keung Ng, Roger Packer, Irene Slavc, Christine Haberler, Matthias Preusser, Tobey J. Macdonald, Paula Z. Proszek, Debbie Hughes, Marc K. Rosenblum, Stephen W. Gilheeney, Ira J. Dunkel, Martin Sill, Simon P. Robinson, Jessica K.R. Boult, Rachael Natrajan, Claire Cairns, Bassel Zebian, Christopher Chandler, Safa Al-Sarraj, Lawrence J. Doey, Andrew J. Martin, Leslie Bridges, Matija Snuderl, David E. Kram, Uwe Kordes, Ulrich Schüller, Jeffrey Knipstein, Stephen Crosier, Mellissa Maybury, Catherine Rowe, Kathreena M. Kurian, Michael Hubank, Ji Wen, Wilda Orisme, James D. Dalton, Kelly Haupfear, Mark Kristiansen, Jane Chalker, Aimee Avery, Amy R. Fairchild, Alex Virasami, Louise Howell, Anna Burford, Valeria Molinari, Diana M. Carvalho, Sara Temelso, Elisa Izquierdo, Iris Stoler, Tejus A. Bale, Scott Newman, Ruth G. Tatevossian, Jessica C. Pickles, Britta Ismer, Alan Mackay, and Matthew Clarke

Abstract

Supplementary Table S3

Published
2023

27. Table S6 from Clinically Tractable Outcome Prediction of Non-WNT/Non-SHH Medulloblastoma Based on TPD52 IHC in a Multicohort Study

Author

Poul H. Sorensen, Michael D. Taylor, Andrey Korshunov, Vijay Ramaswamy, Stefan M. Pfister, Marcel Kool, Andreas von Deimling, David W. Ellison, Damian Stichel, Daniel Schrimpf, Konstantin Okonechnikov, Marina Ryzhova, Andrey Golanov, Olga Zheludkova, Joanna Triscott, Gian Luca Negri, Mariarita Santi, Christopher Dunham, and Alberto Delaidelli

Abstract

Table S6

Published
2023

28. Supplementary Data from Genomic and Expression Profiling of Glioblastoma Stem Cell–Like Spheroid Cultures Identifies Novel Tumor-Relevant Genes Associated with Survival

Author

Bernhard Radlwimmer, Christel Herold-Mende, Peter Lichter, Guido Reifenberger, Andreas Unterberg, Anna Starzinski-Powitz, Benito Campos, Sebastian Barbus, Jochen Hess, Moritz Durchdewald, Heike Peterziel, Michael Sabel, Jörg Felsberg, Christian Hartmann, Felix Engel, Andrey Korshunov, Natalia Becker, Rezvan Ahmadi, Stefanie Hofmann, and Aurélie Ernst

Abstract

Supplementary Data from Genomic and Expression Profiling of Glioblastoma Stem Cell–Like Spheroid Cultures Identifies Novel Tumor-Relevant Genes Associated with Survival

Published
2023

29. Supplementary Figure 5 from Spinal Myxopapillary Ependymomas Demonstrate a Warburg Phenotype

Author

Michael D. Taylor, Gelareh Zadeh, Nada Jabado, Joanna J. Philips, Tarik Tihan, Melike Pekmezci, Andrey Korshunov, Stefan M. Pfister, James T. Rutka, Sidney Croul, Cynthia Hawkins, Abhijit Guha, William A. Weiss, Nalin Gupta, Boleslaw Lach, Wieslawa Grajkowska, Luca Massimi, Marina Ryzhova, Yuan Thompson, Marc Remke, Vijay Ramaswamy, Mark Barszczyk, Kory Zayne, Nadia Hill, Hendrik Witt, David J. Shih, Xin Wang, Kelsey C. Bertrand, Sameer Agnihotri, and Stephen C. Mack

Abstract

Supplementary Figure 5. Assessment of citric acid cycle activity by protein expression analysis of PDHE1a.

Published
2023

30. Figure S4 from Clinically Tractable Outcome Prediction of Non-WNT/Non-SHH Medulloblastoma Based on TPD52 IHC in a Multicohort Study

Author

Poul H. Sorensen, Michael D. Taylor, Andrey Korshunov, Vijay Ramaswamy, Stefan M. Pfister, Marcel Kool, Andreas von Deimling, David W. Ellison, Damian Stichel, Daniel Schrimpf, Konstantin Okonechnikov, Marina Ryzhova, Andrey Golanov, Olga Zheludkova, Joanna Triscott, Gian Luca Negri, Mariarita Santi, Christopher Dunham, and Alberto Delaidelli

Abstract

Fig S4. Overall survival analysis by Kaplan Meier plotting of patients with Group 3/4 medulloblastoma (BH cohort), after stratification based on therapeutic approach and TPD52 IHC. Children in A-B were treated with chemotherapy-only protocols. Patients in C were treated with RT + chemotherapy and in D with therapy intensification. Global p value is reported in the figure. Individual p values (TPD52 neg vs TPD52 => 50%) are as follows: A p=0.0039, B p=0.0079, C p=0.0063, D p=0.020.

Published
2023

31. Supplementary Table 1 - 7 from Spinal Myxopapillary Ependymomas Demonstrate a Warburg Phenotype

Author

Michael D. Taylor, Gelareh Zadeh, Nada Jabado, Joanna J. Philips, Tarik Tihan, Melike Pekmezci, Andrey Korshunov, Stefan M. Pfister, James T. Rutka, Sidney Croul, Cynthia Hawkins, Abhijit Guha, William A. Weiss, Nalin Gupta, Boleslaw Lach, Wieslawa Grajkowska, Luca Massimi, Marina Ryzhova, Yuan Thompson, Marc Remke, Vijay Ramaswamy, Mark Barszczyk, Kory Zayne, Nadia Hill, Hendrik Witt, David J. Shih, Xin Wang, Kelsey C. Bertrand, Sameer Agnihotri, and Stephen C. Mack

Abstract

Supplementary Table 1 - 7. Supplementary Table 1: Clinical and histopathological data associated with all spinal ependymomas analyzed in this study, along with molecular subgroup assignment; Supplementary Table 2: Table of all antibodies used in this study, their commercial sources, and dilutions used; Supplementary Table 3: Table of differentially expressed genes between spinal grade II and myxopapillary ependymoma; Supplementary Table 4: Summary of focal amplifications detected in spinal ependymoma by GISTIC2; Supplementary Table 5: Summary of focal deletions detected in spinal ependymoma by GISTIC2; Supplementary Table 6: List of significant pathways enriched by Gene Set Enrichment Analysis in spinal grade II ependymoma; Supplementary Table 7: List of significant pathways enriched by Gene Set Enrichment Analysis in spinal myxopapillary ependymoma

Published
2023

32. Table S6 from The Senescence-associated Secretory Phenotype Mediates Oncogene-induced Senescence in Pediatric Pilocytic Astrocytoma

Author

Till Milde, Olaf Witt, David T.W. Jones, Stefan M. Pfister, Tilman Brummer, Andrey Korshunov, Christel Herold-Mende, Martin U. Schuhmann, Andreas von Deimling, David Capper, Daniela Kuhn, Marcel Kool, Cornelis M. van Tilburg, Ina Oehme, Jan Gronych, Stefan Pusch, Daniel Picard, Marc Remke, Annika K. Wefers, J.P. Martinez-Barbera, Alexander C. Sommerkamp, Britta Ismer, Diren Usta, Dennis Riehl, Johannes Ridinger, Felix Sahm, Jonas Ecker, Romain Guiho, Thomas Hielscher, Florian Selt, and Juliane L. Buhl

Abstract

Uni-and multivariate Analysis of IL1B and SASP in PA cohort

Published
2023

33. Data from HDAC5 and HDAC9 in Medulloblastoma: Novel Markers for Risk Stratification and Role in Tumor Cell Growth

Author

Olaf Witt, Stefan Pfister, Andreas von Deimling, Michael D. Taylor, Marco Lodrini, Hedwig E. Deubzer, Paul Northcott, Marc Remke, Annette Kopp-Schneider, Andrey Korshunov, Ina Oehme, and Till Milde

Abstract

Purpose: Medulloblastomas are the most common malignant brain tumors in childhood. Survivors suffer from high morbidity because of therapy-related side effects. Thus, therapies targeting tumors in a specific manner with small molecules such as histone deacetylase (HDAC) inhibitors are urgently warranted. This study investigated the expression levels of individual human HDAC family members in primary medulloblastoma samples, their potential as risk stratification markers, and their roles in tumor cell growth.Experimental Design: Gene expression arrays were used to screen for HDAC1 through HDAC11. Using quantitative real time reverse transcriptase-PCR and immunohistochemistry, we studied the expression of HDAC5 and HDAC9 in primary medulloblastoma samples. In addition, we conducted functional studies using siRNA-mediated knockdown of HDAC5 and HDAC9 in medulloblastoma cells.Results: HDAC5 and HDAC9 showed the highest expression in prognostically poor subgroups. This finding was validated in an independent set of medulloblastoma samples. High HDAC5 and HDAC9 expression was significantly associated with poor overall survival, with high HDAC5 and HDAC9 expression posing an independent risk factor. Immunohistochemistry revealed a strong expression of HDAC5 and HDAC9 proteins in most of all primary medulloblastomas investigated. siRNA-mediated knockdown of HDAC5 or HDAC9 in medulloblastoma cells resulted in decreased cell growth and cell viability.Conclusion: HDAC5 and HDAC9 are significantly upregulated in high-risk medulloblastoma in comparison with low-risk medulloblastoma, and their expression is associated with poor survival. Thus, HDAC5 and HDAC9 may be valuable markers for risk stratification. Because our functional studies point toward a role in medulloblastoma cell growth, HDAC5 and HDAC9 may potentially be novel drug targets. Clin Cancer Res; 16(12); 3240–52. ©2010 AACR.

Published
2023

34. Supplemental Table Legend from The Senescence-associated Secretory Phenotype Mediates Oncogene-induced Senescence in Pediatric Pilocytic Astrocytoma

Author

Till Milde, Olaf Witt, David T.W. Jones, Stefan M. Pfister, Tilman Brummer, Andrey Korshunov, Christel Herold-Mende, Martin U. Schuhmann, Andreas von Deimling, David Capper, Daniela Kuhn, Marcel Kool, Cornelis M. van Tilburg, Ina Oehme, Jan Gronych, Stefan Pusch, Daniel Picard, Marc Remke, Annika K. Wefers, J.P. Martinez-Barbera, Alexander C. Sommerkamp, Britta Ismer, Diren Usta, Dennis Riehl, Johannes Ridinger, Felix Sahm, Jonas Ecker, Romain Guiho, Thomas Hielscher, Florian Selt, and Juliane L. Buhl

Abstract

Supplemental Table Legend

Published
2023

35. Supplementary Data from Genetic Aberrations Leading to MAPK Pathway Activation Mediate Oncogene-Induced Senescence in Sporadic Pilocytic Astrocytomas

Author

Nada Jabado, Uri Tabori, Stefan M. Pfister, V. Peter Collins, Andrey Korshunov, Cynthia Hawkins, Jeffrey Atkinson, Jose-Luis Montes, Jean-Pierre Farmer, Laszlo Bognar, Almos Klekner, Peter Hauser, Miklos Garami, Damien Faury, Margret Shirinian, Catherine Vezina, Olaf Witt, Steffen Albrecht, Sally Lambert, Hendrik Witt, David T.W. Jones, Dongh-Anh Quang-Khuong, and Karine Jacob

Abstract

Supplementary Figures S1-S3; Supplementary Tables S1-S2.

Published
2023

36. Supplementary Figure 1 from Spinal Myxopapillary Ependymomas Demonstrate a Warburg Phenotype

Author

Michael D. Taylor, Gelareh Zadeh, Nada Jabado, Joanna J. Philips, Tarik Tihan, Melike Pekmezci, Andrey Korshunov, Stefan M. Pfister, James T. Rutka, Sidney Croul, Cynthia Hawkins, Abhijit Guha, William A. Weiss, Nalin Gupta, Boleslaw Lach, Wieslawa Grajkowska, Luca Massimi, Marina Ryzhova, Yuan Thompson, Marc Remke, Vijay Ramaswamy, Mark Barszczyk, Kory Zayne, Nadia Hill, Hendrik Witt, David J. Shih, Xin Wang, Kelsey C. Bertrand, Sameer Agnihotri, and Stephen C. Mack

Abstract

Supplementary Figure 1. Unsupervised consensus hierarchical clustering and non-negative matrix factorization of 35 spinal ependymoma gene expression signatures from a rank 2 to 4 classification.

Published
2023

37. Supplementary Table S1 from The Transcription Factor Evi-1 Is Overexpressed, Promotes Proliferation, and Is Prognostically Unfavorable in Infratentorial Ependymomas

Author

Martin Hasselblatt, Werner Paulus, Stefan Pfister, Barbara Riesmeier, Andrey Korshunov, Rudi Beschorner, Jörg Felsberg, Sonja Mertsch, Hendrik Witt, Sebastian Bender, and Björn Koos

Abstract

Supplementary Table S1 from The Transcription Factor Evi-1 Is Overexpressed, Promotes Proliferation, and Is Prognostically Unfavorable in Infratentorial Ependymomas

Published
2023

39. Data from Genomic and Expression Profiling of Glioblastoma Stem Cell–Like Spheroid Cultures Identifies Novel Tumor-Relevant Genes Associated with Survival

Author

Bernhard Radlwimmer, Christel Herold-Mende, Peter Lichter, Guido Reifenberger, Andreas Unterberg, Anna Starzinski-Powitz, Benito Campos, Sebastian Barbus, Jochen Hess, Moritz Durchdewald, Heike Peterziel, Michael Sabel, Jörg Felsberg, Christian Hartmann, Felix Engel, Andrey Korshunov, Natalia Becker, Rezvan Ahmadi, Stefanie Hofmann, and Aurélie Ernst

Abstract

Purpose: Glioblastoma spheroid cultures are enriched in tumor stem-like cells and therefore may be more representative of the respective primary tumors than conventional monolayer cultures. We exploited the glioma spheroid culture model to find novel tumor-relevant genes.Experimental Design: We carried out array-based comparative genomic hybridization of spheroid cultures derived from 20 glioblastomas. Microarray-based gene expression analysis was applied to determine genes with differential expression compared with normal brain tissue and to nonneoplastic brain spheroids in glioma spheroid cultures. The protein expression levels of three candidates were determined by immunohistochemistry on tissue microarrays and correlated with clinical outcome. Functional analysis of PDPN was done.Results: Genomic changes in spheroid cultures closely resembled those detected in primary tumors of the corresponding patients. In contrast, genomic changes in serum-grown monolayer cultures established from the same patients did not match well with the respective primary tumors. Microarray-based gene expression analysis of glioblastoma spheroid cultures identified a set of novel candidate genes being upregulated or downregulated relative to normal brain. Quantitative real-time PCR analyses of 8 selected candidate genes in 20 clinical glioblastoma samples validated the microarray findings. Immunohistochemistry on tissue microarrays revealed that expression of AJAP1, EMP3, and PDPN was significantly associated with overall survival of astrocytic glioma patients. Invasive capacity and RhoA activity were decreased in PDPN-silenced spheroids.Conclusion: We identified a set of novel candidate genes that likely play a role in glioblastoma pathogenesis and implicate AJAP1, EMP3, and PDPN as molecular markers associated with the clinical outcome of glioma patients. (Clin Cancer Res 2009;15(21):6541–50)

Published
2023

40. Table S1 from The Senescence-associated Secretory Phenotype Mediates Oncogene-induced Senescence in Pediatric Pilocytic Astrocytoma

Author

Till Milde, Olaf Witt, David T.W. Jones, Stefan M. Pfister, Tilman Brummer, Andrey Korshunov, Christel Herold-Mende, Martin U. Schuhmann, Andreas von Deimling, David Capper, Daniela Kuhn, Marcel Kool, Cornelis M. van Tilburg, Ina Oehme, Jan Gronych, Stefan Pusch, Daniel Picard, Marc Remke, Annika K. Wefers, J.P. Martinez-Barbera, Alexander C. Sommerkamp, Britta Ismer, Diren Usta, Dennis Riehl, Johannes Ridinger, Felix Sahm, Jonas Ecker, Romain Guiho, Thomas Hielscher, Florian Selt, and Juliane L. Buhl

Abstract

Primers and antibodies

Published
2023

41. Table S4 from The Senescence-associated Secretory Phenotype Mediates Oncogene-induced Senescence in Pediatric Pilocytic Astrocytoma

Author

Till Milde, Olaf Witt, David T.W. Jones, Stefan M. Pfister, Tilman Brummer, Andrey Korshunov, Christel Herold-Mende, Martin U. Schuhmann, Andreas von Deimling, David Capper, Daniela Kuhn, Marcel Kool, Cornelis M. van Tilburg, Ina Oehme, Jan Gronych, Stefan Pusch, Daniel Picard, Marc Remke, Annika K. Wefers, J.P. Martinez-Barbera, Alexander C. Sommerkamp, Britta Ismer, Diren Usta, Dennis Riehl, Johannes Ridinger, Felix Sahm, Jonas Ecker, Romain Guiho, Thomas Hielscher, Florian Selt, and Juliane L. Buhl

Abstract

Clinical annotations of the PA patient cohort

Published
2023

42. Table S2 from The Senescence-associated Secretory Phenotype Mediates Oncogene-induced Senescence in Pediatric Pilocytic Astrocytoma

Author

Till Milde, Olaf Witt, David T.W. Jones, Stefan M. Pfister, Tilman Brummer, Andrey Korshunov, Christel Herold-Mende, Martin U. Schuhmann, Andreas von Deimling, David Capper, Daniela Kuhn, Marcel Kool, Cornelis M. van Tilburg, Ina Oehme, Jan Gronych, Stefan Pusch, Daniel Picard, Marc Remke, Annika K. Wefers, J.P. Martinez-Barbera, Alexander C. Sommerkamp, Britta Ismer, Diren Usta, Dennis Riehl, Johannes Ridinger, Felix Sahm, Jonas Ecker, Romain Guiho, Thomas Hielscher, Florian Selt, and Juliane L. Buhl

Abstract

Clinical annotations of the multiplex assay PA cohort and normal brain

Published
2023

43. Supplementary Figure 2 from Spinal Myxopapillary Ependymomas Demonstrate a Warburg Phenotype

Author

Michael D. Taylor, Gelareh Zadeh, Nada Jabado, Joanna J. Philips, Tarik Tihan, Melike Pekmezci, Andrey Korshunov, Stefan M. Pfister, James T. Rutka, Sidney Croul, Cynthia Hawkins, Abhijit Guha, William A. Weiss, Nalin Gupta, Boleslaw Lach, Wieslawa Grajkowska, Luca Massimi, Marina Ryzhova, Yuan Thompson, Marc Remke, Vijay Ramaswamy, Mark Barszczyk, Kory Zayne, Nadia Hill, Hendrik Witt, David J. Shih, Xin Wang, Kelsey C. Bertrand, Sameer Agnihotri, and Stephen C. Mack

Abstract

Supplementary Figure 2. Summary of focal copy number alterations detected by GISTIC2 in spinal Grade II and Myxopapillary Ependymoma.

Published
2023

44. Table S4 from Clinically Tractable Outcome Prediction of Non-WNT/Non-SHH Medulloblastoma Based on TPD52 IHC in a Multicohort Study

Author

Poul H. Sorensen, Michael D. Taylor, Andrey Korshunov, Vijay Ramaswamy, Stefan M. Pfister, Marcel Kool, Andreas von Deimling, David W. Ellison, Damian Stichel, Daniel Schrimpf, Konstantin Okonechnikov, Marina Ryzhova, Andrey Golanov, Olga Zheludkova, Joanna Triscott, Gian Luca Negri, Mariarita Santi, Christopher Dunham, and Alberto Delaidelli

Abstract

Table S4

Published
2023

45. Table S1 from Clinically Tractable Outcome Prediction of Non-WNT/Non-SHH Medulloblastoma Based on TPD52 IHC in a Multicohort Study

Author

Poul H. Sorensen, Michael D. Taylor, Andrey Korshunov, Vijay Ramaswamy, Stefan M. Pfister, Marcel Kool, Andreas von Deimling, David W. Ellison, Damian Stichel, Daniel Schrimpf, Konstantin Okonechnikov, Marina Ryzhova, Andrey Golanov, Olga Zheludkova, Joanna Triscott, Gian Luca Negri, Mariarita Santi, Christopher Dunham, and Alberto Delaidelli

Abstract

Table S1

Published
2023

47. Data from Nestin Mediates Hedgehog Pathway Tumorigenesis

Author

Zeng-jie Yang, Tom Curran, Stefan M. Pfister, Andrey Korshunov, Jinhua Wu, Hao Zhang, Jessica M.Y. Ng, Yongqiang Liu, Larra W. Yuelling, Renata E. Gordon, Fang Du, Eric H. Lee, and Peng Li

Abstract

The intermediate filament protein Nestin serves as a biomarker for stem cells and has been used to identify subsets of cancer stem–like cells. However, the mechanistic contributions of Nestin to cancer pathogenesis are not understood. Here, we report that Nestin binds the hedgehog pathway transcription factor Gli3 to mediate the development of medulloblastomas of the hedgehog subtype. In a mouse model system, Nestin levels increased progressively during medulloblastoma formation, resulting in enhanced tumor growth. Conversely, loss of Nestin dramatically inhibited proliferation and promoted differentiation. Mechanistic investigations revealed that the tumor-promoting effects of Nestin were mediated by binding to Gli3, a zinc finger transcription factor that negatively regulates hedgehog signaling. Nestin binding to Gli3 blocked Gli3 phosphorylation and its subsequent proteolytic processing, thereby abrogating its ability to negatively regulate the hedgehog pathway. Our findings show how Nestin drives hedgehog pathway–driven cancers and uncover in Gli3 a therapeutic target to treat these malignancies. Cancer Res; 76(18); 5573–83. ©2016 AACR.

Published
2023

48. Table S2 from Clinically Tractable Outcome Prediction of Non-WNT/Non-SHH Medulloblastoma Based on TPD52 IHC in a Multicohort Study

Author

Poul H. Sorensen, Michael D. Taylor, Andrey Korshunov, Vijay Ramaswamy, Stefan M. Pfister, Marcel Kool, Andreas von Deimling, David W. Ellison, Damian Stichel, Daniel Schrimpf, Konstantin Okonechnikov, Marina Ryzhova, Andrey Golanov, Olga Zheludkova, Joanna Triscott, Gian Luca Negri, Mariarita Santi, Christopher Dunham, and Alberto Delaidelli

Abstract

List of differentially expressed proteins between Group 3 and Group 4 medulloblastoma in the Archer (3) and Forget (4) datasets.

Published
2023

49. Table S5 from Clinically Tractable Outcome Prediction of Non-WNT/Non-SHH Medulloblastoma Based on TPD52 IHC in a Multicohort Study

Author

Poul H. Sorensen, Michael D. Taylor, Andrey Korshunov, Vijay Ramaswamy, Stefan M. Pfister, Marcel Kool, Andreas von Deimling, David W. Ellison, Damian Stichel, Daniel Schrimpf, Konstantin Okonechnikov, Marina Ryzhova, Andrey Golanov, Olga Zheludkova, Joanna Triscott, Gian Luca Negri, Mariarita Santi, Christopher Dunham, and Alberto Delaidelli

Abstract

Table S5

Published
2023

50. Figure S3 from Clinically Tractable Outcome Prediction of Non-WNT/Non-SHH Medulloblastoma Based on TPD52 IHC in a Multicohort Study

Author

Poul H. Sorensen, Michael D. Taylor, Andrey Korshunov, Vijay Ramaswamy, Stefan M. Pfister, Marcel Kool, Andreas von Deimling, David W. Ellison, Damian Stichel, Daniel Schrimpf, Konstantin Okonechnikov, Marina Ryzhova, Andrey Golanov, Olga Zheludkova, Joanna Triscott, Gian Luca Negri, Mariarita Santi, Christopher Dunham, and Alberto Delaidelli

Abstract

Fig S3. A) Density plot representing the distribution of the percentage of positive cell for tumors in the BH cohort. As described in the manuscript text, three broad categories of tumors were identified: TPD52 negative (no positive cells, 54.9% of tumors), TPD52 low (=> 20 % and < 50% positive cells, 34.1% of tumors), or TPD52 high (=> 50% positive cells, 11.0% of tumors) B) Density plot representing the distribution of tumors in the BH cohort according to TPD52 mRNA expression. Two broad categories of tumors can be identified: TPD52 low (mostly corresponding to tumors TPD52 negative by IHC) and TPD52 high (mostly corresponding to IHC positive tumors). C) Heatmap and contingency table representing the correlation between high TPD52 mRNA expression and IHC positivity for the cases in the BH cohort. D) Maximally selected rank statistics analysis of the optimal TPD52 percentage cut-off for univariate survival analysis. Higher values on the y axis indicate lower log-rank p values in univariate survival analysis. Significance level according to the improved Bonferroni inequality corresponds to y < 0.001, so every possible cut-off for TPD52 percentage positivity results in significant differences in univariate survival analysis. The optimal cut-off (> 40% positive cells = high) corresponds to the => 50% cut-off utilized in Figs 2D-F. E) Representative IHC pictures for tumors negative, or with < 50% and => 50% positive cells. Scale bar = 50 um. TPD52 IHC was not prognostic in SHH tumors.

Published
2023

Catalog

Books, media, physical & digital resources
See catalog results