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1. Diffuse pediatric high-grade glioma of methylation-based RTK2A and RTK2B subclasses present distinct radiological and histomolecular features including Gliomatosis cerebri phenotype

Author

Tauziède-Espariat, Arnault, Friker, Lea L., Nussbaumer, Gunther, Bison, Brigitte, Dangouloff-Ros, Volodia, Métais, Alice, Sumerauer, David, Zamecnik, Josef, Benesch, Martin, Perwein, Thomas, van Vuurden, Dannis, Wesseling, Pieter, La Madrid, Andrés Morales, Garrè, Maria Luisa, Antonelli, Manila, Giangaspero, Felice, Pietsch, Torsten, Sturm, Dominik, Jones, David T. W., Pfister, Stefan M., Grabovska, Yura, Mackay, Alan, Jones, Chris, Grill, Jacques, Ajlil, Yassine, von Bueren, André O., Karremann, Michael, Hoffmann, Marion, Kramm, Christof M., Kwiecien, Robert, Castel, David, Gielen, Gerrit H., and Varlet, Pascale

Published
2024
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2. GABAergic neuronal lineage development determines clinically actionable targets in diffuse hemispheric glioma, H3G34-mutant

Author

Liu, Ilon, Alencastro Veiga Cruzeiro, Gustavo, Bjerke, Lynn, Rogers, Rebecca F., Grabovska, Yura, Beck, Alexander, Mackay, Alan, Barron, Tara, Hack, Olivia A., Quezada, Michael A., Molinari, Valeria, Shaw, McKenzie L., Perez-Somarriba, Marta, Temelso, Sara, Raynaud, Florence, Ruddle, Ruth, Panditharatna, Eshini, Englinger, Bernhard, Mire, Hafsa M., Jiang, Li, Nascimento, Andrezza, LaBelle, Jenna, Haase, Rebecca, Rozowsky, Jacob, Neyazi, Sina, Baumgartner, Alicia-Christina, Castellani, Sophia, Hoffman, Samantha E., Cameron, Amy, Morrow, Murry, Nguyen, Quang-De, Pericoli, Giulia, Madlener, Sibylle, Mayr, Lisa, Dorfer, Christian, Geyeregger, Rene, Rota, Christopher, Ricken, Gerda, Ligon, Keith L., Alexandrescu, Sanda, Cartaxo, Rodrigo T., Lau, Benison, Uphadhyaya, Santhosh, Koschmann, Carl, Braun, Emelie, Danan-Gotthold, Miri, Hu, Lijuan, Siletti, Kimberly, Sundström, Erik, Hodge, Rebecca, Lein, Ed, Agnihotri, Sameer, Eisenstat, David D., Stapleton, Simon, King, Andrew, Bleil, Cristina, Mastronuzzi, Angela, Cole, Kristina A., Waanders, Angela J., Montero Carcaboso, Angel, Schüller, Ulrich, Hargrave, Darren, Vinci, Maria, Carceller, Fernando, Haberler, Christine, Slavc, Irene, Linnarsson, Sten, Gojo, Johannes, Monje, Michelle, Jones, Chris, and Filbin, Mariella G.

Published
2024
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3. The significance of clinico-pathological and molecular sub-groups in Malignant Rhabdoid Tumours

Author

Grabovska, Yura

Subjects
616.99
Abstract

Introduction: Malignant Rhabdoid Tumours (MRT) are aggressive early childhood tumours characterised by biallelic inactivation of SMARCB1. Having the potential to arise in an array of distinct tissues (CNS-located atypical teratoid rhabdoid tumours, ATRT; extra-cranial rhabdoid tumours, ECRT) they are often treated as distinct entities therapeutically and in clinical/biological studies although emerging sub-groups of MRT have provided new understanding of the disease heterogeneity. Lack of consensus on sub-group number and biology can be seen as a hurdle to future studies. Methods: Gene expression and methylation array profiling of primary MRT was performed on clinico-pathologically annotated tumour profiles from UK cancer centres and combined with published MRT data in a meta-analysis. To characterise the common biological features of MRT, regardless of location, differential expression, methylation, gene and pathway analyses were compared to other paediatric embryonal tumour expression and methylation profiles (i.e. Medulloblastoma, Ewings Sarcoma, Rhabdomyosarcoma, Wilms tumour and Neuroblastoma). Survival analysis was carried out on UK MRT samples to identify novel DNA methylation markers associated with disease outcome. Based on evidence suggesting immune system involvement in at least one MRT subgroup, "methylCibersort" a novel in-silico method was used to estimate immune cell infiltration in a large cohort of pan-CNS tumours including MRT. Results: Clustering all MRT together recapitulates the subgroups observed in ATRT alone; broadly overlapping with recently published ATRT and ECRT subgroup models. A putative expanded subgrouping model encompassing all MRT highlights additional heterogeneity and defines novel subgroup characteristics. Subgroup differences were shown to better explain differences in MRT biology than tumour location alone. Survival analysis identified a number of novel survival associations with DNA methylation state. Immune infiltration estimation using methylCibersort identified differences in immune interactions across a large dataset of different CNS tumours, and presented novel prognostic feature. Conclusion: MRT is a complex disease owing both to the rarity of the tumour, resulting in lack of comprehensive genomic profiling, and heterogeneity observed in the tumour biology. This thesis presents evidence to support the definition of MRT as a related tumour type with differences arising due to disease subgroups. In addition, a meta-analysis comparing published subgrouping schemes seeks to direct future research by providing a subgroup consensus encompassing all MRT. Novel survival associations and immune infiltration estimates provide new avenues for further research.

Published
2020

4. Medulloblastoma group 3 and 4 tumors comprise a clinically and biologically significant expression continuum reflecting human cerebellar development

Author

Williamson, Daniel, Schwalbe, Edward C., Hicks, Debbie, Aldinger, Kimberly A., Lindsey, Janet C., Crosier, Stephen, Richardson, Stacey, Goddard, Jack, Hill, Rebecca M., Castle, Jemma, Grabovska, Yura, Hacking, James, Pizer, Barry, Wharton, Stephen B., Jacques, Thomas S., Joshi, Abhijit, Bailey, Simon, and Clifford, Steven C.

Published
2022
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5. An exceptionally rare case of a diffuse midline glioma with concomitant H3.1 K27M and G34R mutations in the HIST1H3C (H3C3) gene.

Author

Reisz, Zita, Pereira, Rita, Nevis, Smitha, Mackay, Alan, Bhaw, Leena, Grabovska, Yura, Laxton, Ross, Molinari, Valeria, Burford, Anna, Clark, Barnaby, Bleil, Cristina, Zebian, Bassel, Pace, Erika, Weiser, Annette, Carceller, Fernando, Marshall, Lynley, King, Andrew, Bodi, Istvan, Al-Sarraj, Safa, and Jones, Chris

Subjects
MEDICAL sciences, BRAIN tumors, WHOLE genome sequencing, MAGNETIC resonance imaging, DNA methylation
Abstract

Histone mutations (H3 K27M, H3 G34R/V) are molecular features defining subtypes of paediatric-type diffuse high-grade gliomas (HGG) (diffuse midline glioma (DMG), H3 K27-altered, diffuse hemispheric glioma (DHG), H3 G34-mutant). The WHO classification recognises in exceptional cases, these mutations co-occur. We report one such case of a 2-year-old female presenting with neurological symptoms; MRI imaging identified a brainstem lesion which was biopsied. Histology showed diffusely infiltrating pleomorphic astrocytes, multinucleated cells, and conspicuous mitotic activity; the diagnosis was DMG, H3 K27-altered (immunohistochemistry: H3K27me3 loss, H3K27M positivity). DNA methylation profiling (Illumina EPIC BeadArrays, brain tumour classifier (MNP v12.5 R package)) classified the tumour as 'DMG, H3 K27-altered' (calibrated score = 0.99). Further molecular studies (whole exome, whole genome sequencing) revealed concurrent H3.1 K27M and G34R mutations (clonal, in the same reads) of H3C3, FGF11 and PIK3CA somatic variants, and a pathogenic germline NBN variant. The RNAseq profile clustered with H3K27M-mutant tumours. A patient-derived cell culture was established enabling unbiased in vitro drug screening; no selective sensitivities were identified. Chromatin immunoprecipitation assays with sequencing (ChIP-seq; H3K27ac, H3K27me3, H3K36me3, RNApol2 marks) showed features in keeping with DMG H3 K27M-mutant tumours (H3K27ac loci including OLIG2, IRX1/2, PKDCC). The patient was treated with adjuvant radiotherapy, but progressed and passed away 13 months post-diagnosis. This case is an exceptionally rare, complex variant of histone-mutant paediatric HGG, illustrating that the H3.1 K27M mutation demonstrates a dominance over the molecular and clinical profiles compared to G34R, and highlights the importance of broad molecular profiling to identify such examples for further study. [ABSTRACT FROM AUTHOR]

Published
2025
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6. Molecular landscape of IDH-mutant primary astrocytoma Grade IV/glioblastomas

Author

Wong, Queenie Hoi-Wing, Li, Kay Ka-Wai, Wang, Wei-Wei, Malta, Tathiane M., Noushmehr, Houtan, Grabovska, Yura, Jones, Chris, Chan, Aden Ka-Yin, Kwan, Johnny Sheung-Him, Huang, Queenie Jun-Qi, Wong, Gabriel Chun-Hei, Li, Wen-Cai, Liu, Xian-Zhi, Chen, Hong, Chan, Danny Tat-Ming, Mao, Ying, Zhang, Zhen-Yu, Shi, Zhi-Feng, and Ng, Ho-Keung

Published
2021
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7. Gliomatosis cerebri in children: A poor prognostic phenotype of diffuse gliomas with a distinct molecular profile.

Author

Nussbaumer, Gunther, Benesch, Martin, Grabovska, Yura, Mackay, Alan, Castel, David, Grill, Jacques, Alonso, Marta M, Antonelli, Manila, Bailey, Simon, Baugh, Joshua N, Biassoni, Veronica, Blattner-Johnson, Mirjam, Broniscer, Alberto, Carai, Andrea, Colafati, Giovanna Stefania, Colditz, Niclas, Corbacioglu, Selim, Crampsie, Shauna, Entz-Werle, Natacha, and Eyrich, Matthias

Published
2024
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9. Gliomatosis cerebri in children:A poor prognostic phenotype of diffuse gliomas with a distinct molecul profile

Author

Nussbaumer, Gunther, Benesch, Martin, Grabovska, Yura, Mackay, Alan, Castel, David, Grill, Jacques, Alonso, Marta M., Antonelli, Manila, Bailey, Simon, Baugh, Joshua N., Biassoni, Veronica, Blattner-Johnson, Mirjam, Broniscer, Alberto, Carai, Andrea, Colafati, Giovanna Stefania, Colditz, Niclas, Corbacioglu, Selim, Crampsie, Shauna, Entz-Werle, Natacha, Eyrich, Matthias, Friker, Lea L., Frühwald, Michael C., Garrè, Maria Luisa, Gerber, Nicolas U., Giangaspero, Felice, Gil-Da-Costa, Maria J., Graf, Norbert, Hargrave, Darren, Hauser, Peter, Herrlinger, Ulrich, Hoffmann, Marion, Hulleman, Esther, Izquierdo, Elisa, Jacobs, Sandra, Karremann, Michael, Kattamis, Antonis, Kebudi, Rejin, Kortmann, Rolf Dieter, Kwiecien, Robert, Massimino, Maura, Mastronuzzi, Angela, Miele, Evelina, Morana, Giovanni, Noack, Claudia M., Pentikainen, Virve, Perwein, Thomas, Pfister, Stefan M., Pietsch, Torsten, Roka, Kleoniki, Rossi, Sabrina, Rutkowski, Stefan, Schiavello, Elisabetta, Seidel, Clemens, Štěrba, Jaroslav, Sturm, Dominik, Sumerauer, David, Tacke, Anna, Temelso, Sara, Valentini, Chiara, van Vuurden, Dannis, Varlet, Pascale, Veldhuijzen van Zanten, Sophie E.M., Vinci, Maria, von Bueren, André O., Warmuth-Metz, Monika, Wesseling, Pieter, Wiese, Maria, Wolff, Johannes E.A., Zamecnik, Josef, La Madrid, Andrés Morales, Bison, Brigitte, Gielen, Gerrit H., Jones, David T.W., Jones, Chris, Kramm, Christof M., Nussbaumer, Gunther, Benesch, Martin, Grabovska, Yura, Mackay, Alan, Castel, David, Grill, Jacques, Alonso, Marta M., Antonelli, Manila, Bailey, Simon, Baugh, Joshua N., Biassoni, Veronica, Blattner-Johnson, Mirjam, Broniscer, Alberto, Carai, Andrea, Colafati, Giovanna Stefania, Colditz, Niclas, Corbacioglu, Selim, Crampsie, Shauna, Entz-Werle, Natacha, Eyrich, Matthias, Friker, Lea L., Frühwald, Michael C., Garrè, Maria Luisa, Gerber, Nicolas U., Giangaspero, Felice, Gil-Da-Costa, Maria J., Graf, Norbert, Hargrave, Darren, Hauser, Peter, Herrlinger, Ulrich, Hoffmann, Marion, Hulleman, Esther, Izquierdo, Elisa, Jacobs, Sandra, Karremann, Michael, Kattamis, Antonis, Kebudi, Rejin, Kortmann, Rolf Dieter, Kwiecien, Robert, Massimino, Maura, Mastronuzzi, Angela, Miele, Evelina, Morana, Giovanni, Noack, Claudia M., Pentikainen, Virve, Perwein, Thomas, Pfister, Stefan M., Pietsch, Torsten, Roka, Kleoniki, Rossi, Sabrina, Rutkowski, Stefan, Schiavello, Elisabetta, Seidel, Clemens, Štěrba, Jaroslav, Sturm, Dominik, Sumerauer, David, Tacke, Anna, Temelso, Sara, Valentini, Chiara, van Vuurden, Dannis, Varlet, Pascale, Veldhuijzen van Zanten, Sophie E.M., Vinci, Maria, von Bueren, André O., Warmuth-Metz, Monika, Wesseling, Pieter, Wiese, Maria, Wolff, Johannes E.A., Zamecnik, Josef, La Madrid, Andrés Morales, Bison, Brigitte, Gielen, Gerrit H., Jones, David T.W., Jones, Chris, and Kramm, Christof M.

Abstract

Background: The term gliomatosis cerebri (GC), a radiology-defined highly infiltrating diffuse glioma, has been abandoned since molecular GC-associated features could not be established. Methods: We conducted a multinational retrospective study of 104 children and adolescents with GC providing comprehensive clinical and (epi-)genetic characterization. Results: Median overall survival (OS) was 15.5 months (interquartile range, 10.9–27.7) with a 2-year survival rate of 28%. Histopathological grading correlated significantly with median OS: CNS WHO grade II: 47.8 months (25.2–55.7); grade III: 15.9 months (11.4–26.3); grade IV: 10.4 months (8.8–14.4). By DNA methylation profiling (n = 49), most tumors were classified as pediatric-type diffuse high-grade glioma (pedHGG), H3-/IDH-wild-type (n = 31/49, 63.3%) with enriched subclasses pedHGG_RTK2 (n = 19), pedHGG_A/B (n = 6), and pedHGG_MYCN (n = 5), but only one pedHGG_RTK1 case. Within the pedHGG, H3-/IDH-wild-type subgroup, recurrent alterations in EGFR (n = 10) and BCOR (n = 9) were identified. Additionally, we observed structural aberrations in chromosome 6 in 16/49 tumors (32.7%) across tumor types. In the pedHGG, H3-/IDH-wild-type subgroup TP53 alterations had a significant negative effect on OS. Conclusions: Contrary to previous studies, our representative pediatric GC study provides evidence that GC has a strong predilection to arise on the background of specific molecular features (especially pedHGG_ RTK2, pedHGG_A/B, EGFR and BCOR mutations, chromosome 6 rearrangements).

Published
2024

10. P-179 Altered lipid metabolism in IMiD/CELMoD resistant multiple myeloma confers novel and targetable vulnerabilities

Author

Bird, Sarah, primary, Xu, Yitao, additional, Sialana, Fernando, additional, Licciardello, Marco, additional, Che, Harvey, additional, Tamin, Saleh, additional, Bouguenina, Habib, additional, Grabovska, Yura, additional, Liu, Enze, additional, Morales, Salomon, additional, Chrisochoidou, Yakinthi, additional, Li, Yigen, additional, Martin, Shannon, additional, Wilson, Amy, additional, Flynt, Erin, additional, Walker, Brian, additional, Choudhary, Jyoti, additional, Clarke, Paul, additional, Keun, Hector, additional, and Pawlyn, Charlotte, additional

Published
2023
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12. Pediatric pan-central nervous system tumor analysis of immune-cell infiltration identifies correlates of antitumor immunity

Author

Grabovska, Yura, Mackay, Alan, O’Hare, Patricia, Crosier, Stephen, Finetti, Martina, Schwalbe, Edward C., Pickles, Jessica C., Fairchild, Amy R., Avery, Aimee, Cockle, Julia, Hill, Rebecca, Lindsey, Janet, Hicks, Debbie, Kristiansen, Mark, Chalker, Jane, Anderson, John, Hargrave, Darren, Jacques, Thomas S., Straathof, Karin, Bailey, Simon, Jones, Chris, Clifford, Steven C., and Williamson, Daniel

Published
2020
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13. HGG-17. SINGLE-CELL AND SPATIAL ANALYSES DECIPHER THE UNIQUE INVASIVE GROWTH PATTERN OF GLIOMATOSIS CEREBRI

Author

Crampsie, Shauna, primary, Liu, Ilon, additional, Petrilli, Lucia Lisa, additional, Mackay, Alan, additional, Spinozzi, Giulio, additional, Grabovska, Yura, additional, Hack, Olivia A, additional, Kessler, Ketty, additional, Temelso, Sara, additional, Carvalho, Diana Martins, additional, Burford, Anna, additional, Sejdiu, Drenusha, additional, Molinari, Valeria, additional, Shaw, McKenzie L, additional, Mire, Hafsa M, additional, Pericoli, Giulia, additional, Cerimele, Alfredo, additional, Barry, Clémentine, additional, Cocito, Carolina, additional, Debily, Marie-Anne, additional, Kergrohen, Thomas, additional, Ajlil, Yassine, additional, Beccaria, Kévin, additional, Varlet, Pascale, additional, Tauziède-Espariat, Arnault, additional, Mastronuzzi, Angela, additional, Carai, Andrea, additional, Giovannoni, Isabella, additional, Rossi, Sabrina, additional, Miele, Evelina, additional, Grill, Jacques, additional, Jacques, Thomas S, additional, Greenfield, Jeffery P, additional, Castel, David, additional, Vinci, Maria, additional, Filbin, Mariella G, additional, and Jones, Chris, additional

Published
2023
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15. Data from DIPG Harbors Alterations Targetable by MEK Inhibitors, with Acquired Resistance Mechanisms Overcome by Combinatorial Inhibition

Author

Izquierdo, Elisa, primary, Carvalho, Diana M., primary, Mackay, Alan, primary, Temelso, Sara, primary, Boult, Jessica K.R., primary, Pericoli, Giulia, primary, Fernandez, Elisabet, primary, Das, Molina, primary, Molinari, Valeria, primary, Grabovska, Yura, primary, Rogers, Rebecca F., primary, Ajmone-Cat, Maria Antonietta, primary, Proszek, Paula Z., primary, Stubbs, Mark, primary, Depani, Sarita, primary, O'Hare, Patricia, primary, Yu, Lu, primary, Roumelioti, Georgia, primary, Choudhary, Jyoti S., primary, Clarke, Matthew, primary, Fairchild, Amy R., primary, Jacques, Thomas S., primary, Grundy, Richard G., primary, Howell, Lisa, primary, Picton, Susan, primary, Adamski, Jenny, primary, Wilson, Shaun, primary, Gray, Juliet C., primary, Zebian, Bassel, primary, Marshall, Lynley V., primary, Carceller, Fernando, primary, Grill, Jacques, primary, Vinci, Maria, primary, Robinson, Simon P., primary, Hubank, Michael, primary, Hargrave, Darren, primary, and Jones, Chris, primary

Published
2023
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16. Supplementary Data from DIPG Harbors Alterations Targetable by MEK Inhibitors, with Acquired Resistance Mechanisms Overcome by Combinatorial Inhibition

Author

Izquierdo, Elisa, primary, Carvalho, Diana M., primary, Mackay, Alan, primary, Temelso, Sara, primary, Boult, Jessica K.R., primary, Pericoli, Giulia, primary, Fernandez, Elisabet, primary, Das, Molina, primary, Molinari, Valeria, primary, Grabovska, Yura, primary, Rogers, Rebecca F., primary, Ajmone-Cat, Maria Antonietta, primary, Proszek, Paula Z., primary, Stubbs, Mark, primary, Depani, Sarita, primary, O'Hare, Patricia, primary, Yu, Lu, primary, Roumelioti, Georgia, primary, Choudhary, Jyoti S., primary, Clarke, Matthew, primary, Fairchild, Amy R., primary, Jacques, Thomas S., primary, Grundy, Richard G., primary, Howell, Lisa, primary, Picton, Susan, primary, Adamski, Jenny, primary, Wilson, Shaun, primary, Gray, Juliet C., primary, Zebian, Bassel, primary, Marshall, Lynley V., primary, Carceller, Fernando, primary, Grill, Jacques, primary, Vinci, Maria, primary, Robinson, Simon P., primary, Hubank, Michael, primary, Hargrave, Darren, primary, and Jones, Chris, primary

Published
2023
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17. Abstract 3879: SETD2 is a novel and druggable dependency in IMiD/CELMoD resistant multiple myeloma models

Author

Bird, Sarah Anne, primary, Licciardello, Marco, additional, Chrisochoidou, Yakinthi, additional, Smith, James, additional, Barber, Amy, additional, Cheung, Jack, additional, Grabovska, Yura, additional, Martin, Shannon, additional, Sialana, Fernando, additional, Che, Harvey, additional, Bouguenina, Habib, additional, Bellenie, Benjamin, additional, Walker, Brian, additional, Clarke, Paul, additional, and Pawlyn, Charlotte, additional

Published
2023
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18. Inter and intra-tumor heterogeneity of paediatric type diffuse high-grade gliomas revealed by single-cell mass cytometry

Author

Petrilli, Lucia Lisa, primary, Fuoco, Claudia, additional, Palma, Alessandro, additional, Pasquini, Luca, additional, Pericoli, Giulia, additional, Grabovska, Yura, additional, Mackay, Alan, additional, Rossi, Sabrina, additional, Carcaboso, Angel M., additional, Carai, Andrea, additional, Mastronuzzi, Angela, additional, Jones, Chris, additional, Cesareni, Gianni, additional, Locatelli, Franco, additional, and Vinci, Maria, additional

Published
2022
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19. Multiomics Analysis of IMiD/CELMoD Resistant Multiple Myeloma Models Uncovers Novel and Targetable Vulnerabilities in the SREBP Lipid Synthesis Pathway

Author

Bird, Sarah A., primary, Barber, Amy, additional, Sialana, Fernando J., additional, Licciardello, Marco P., additional, Che, Harvey, additional, Bouguenina, Habib, additional, Grabovska, Yura, additional, Liu, Enze, additional, Chrisochoidou, Yakinthi, additional, Martin, Shannon, additional, Choudhary, Jyoti, additional, Walker, Brian A., additional, Collins, Ian, additional, Clarke, Paul, additional, and Pawlyn, Charlotte, additional

Published
2022
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20. EPCO-24. MULTI-OMIC PROFILING OF PATIENT-DERIVED SUBCLONES IDENTIFIES AGGRESSIVE CELLULAR SUBPOPULATIONS IN PAEDIATRIC DIFFUSE HIGH GRADE GLIOMAS (PDHGGS)

Author

Kessler, Ketty, primary, Grabovska, Yura, additional, Burford, Anna, additional, Temelso, Sara, additional, Tari, Haider, additional, Molinari, Valeria, additional, Crampsie, Shauna, additional, Yu, Lu, additional, Choudhary, Jyoti, additional, Proszek, Paula, additional, Hubank, Mike, additional, Mackay, Alan, additional, and Jones, Chris, additional

Published
2022
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22. Medulloblastoma Group 3 and 4 Tumors Comprise a Clinically and Biologically Significant Expression Continuum Reflecting Human Cerebellar Development

Author

Williamson, Daniel, primary, Schwalbe, Edward C, additional, Hicks, Debbie, additional, Aldinger, Kimberly A, additional, Lindsey, Janet C, additional, Crosier, Stephen, additional, Richardson, Stacey, additional, Goddard, Jack, additional, Hill, Rebecca M, additional, Castle, Jemma, additional, Grabovska, Yura, additional, Hacking, James, additional, Pizer, Barry, additional, Wharton, Stephen B, additional, Jacques, Thomas S, additional, Joshi, Abhijit, additional, Bailey, Simon, additional, and Clifford, Steven C, additional

Published
2022
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23. HGG-46. Inter and Intra-tumor Heterogeneity of Pediatric-type Diffuse High-Grade Glioma Revealed by High-Dimensional Single-Cell Proteomics

Author

Petrilli, Lucia Lisa, primary, Fuoco, Claudia, additional, Pasquini, Luca, additional, Palma, Alessandro, additional, Pericoli, Giulia, additional, Grabovska, Yura, additional, Mackay, Alan, additional, Rossi, Sabrina, additional, Camassei, Francesca Diomedi, additional, Carcaboso, Angel Montero, additional, Carai, Andrea, additional, Mastronuzzi, Angela, additional, Jones, Chris, additional, Cesareni, Gianni, additional, Locatelli, Franco, additional, and Vinci, Maria, additional

Published
2022
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24. DIPG-41. Multi-omic profiling of patient-derived subclones identifies aggressive cellular subpopulations in paediatric diffuse high-grade gliomas (PDHGGs)

Author

Kessler, Ketty, primary, Grabovska, Yura, additional, Burford, Anna, additional, Temelso, Sara, additional, Tari, Haider, additional, Molinari, Valeria, additional, Crampsie, Shauna, additional, Yu, Lu, additional, Choudhary, Jyoti, additional, Proszek, Paula, additional, Hubank, Michael, additional, Mackay, Alan, additional, and Jones, Chris, additional

Published
2022
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25. IMMU-12. Exploring and modulating the tumour immune microenvironment to facilitate the selection of immunotherapies for paediatric-type diffuse high-grade glioma

Author

Cockle, Julia, primary, Bjerke, Lynn, additional, Mackay, Alan, additional, Grabovska, Yura, additional, Burford, Anna, additional, Molinari, Valeria, additional, Pereira, Rita, additional, Boult, Jessica, additional, Robinson, Simon, additional, Carvalho, Diana Martins, additional, Clarke, Matthew, additional, Titley, Ian, additional, Yara, Erika, additional, Straathof, Karin, additional, Wennerberg, Erik, additional, Becher, Oren, additional, Castro, Maria, additional, Melcher, Alan, additional, and Jones, Chris, additional

Published
2022
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26. HGG-49. Gliomatosis cerebri in children: A collaborative report from the European Society for Pediatric Oncology (SIOPE)

Author

Nussbaumer, Gunther, primary, Benesch, Martin, additional, Gielen, Gerrit H, additional, Castel, David, additional, Grill, Jacques, additional, Alonso Roldán, Marta M, additional, Antonelli, Manila, additional, Bailey, Simon, additional, Baugh, Joshua N, additional, Biassoni, Veronica, additional, Carai, Andrea, additional, Colditz, Niclas, additional, Colefati, Giovanni Stefania, additional, Corbacioglu, Selim, additional, Crampsie, Shauna, additional, Entz-Werle, Natacha, additional, Eyrich, Matthias, additional, Frühwald, Michael C, additional, Garrè, Maria Luisa, additional, Gerber, Nicolas U, additional, Giangaspero, Felice, additional, Gil-da-Costa, Maria João, additional, Grabovska, Yura, additional, Graf, Norbert, additional, Hargrave, Darren, additional, Hauser, Peter, additional, Hoffmann, Marion, additional, Hulleman, Esther, additional, Jacobs, Sandra, additional, Karremann, Michael, additional, Kattamis, Antonis, additional, Kebudi, Rejin, additional, Kortmann, Rolf-Dieter, additional, Kwiecien, Robert, additional, Mackay, Alan, additional, Massimino, Maura, additional, Miele, Evelina, additional, Mastronuzzi, Angela, additional, Morana, Giovanni, additional, Noack, Claudia M, additional, Pentikainen, Virve, additional, Perwein, Thomas, additional, Pfister, Stefan M, additional, Pietsch, Torsten, additional, Roka, Kleoniki, additional, Rossi, Sabrina, additional, Rutkowski, Stefan, additional, Schiavello, Elisabetta, additional, Štěrba, Jaroslav, additional, Sturm, Dominik, additional, Sumerauer, David, additional, Temelso, Sara, additional, van Vuurden, Dannis, additional, Varlet, Pascale, additional, Veldhuijzen van Zanten, Sophie E M, additional, Vinci, Maria, additional, von Bueren, André O, additional, Warmuth-Metz, Monika, additional, Wesseling, Pieter, additional, Wiese, Maria, additional, Wolff, Johannes E A, additional, Zamecnik, Josef, additional, Jones, David T W, additional, Bison, Brigitte, additional, La Madrid, Andrés Morales, additional, Jones, Chris, additional, and Kramm, Christof M, additional

Published
2022
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27. HGG-42. Evolutionary selection of key oncogenic alterations in patient-derived models of paediatric diffuse high grade glioma (PDHGG) subtypesin vitro andin vivo

Author

Mackay, Alan, primary, Temelso, Sara, additional, Carvalho, Diana, additional, Kessler, Ketty, additional, Boult, Jessica, additional, Izquierdo, Elisa, additional, Pereira, Rita, additional, Potente, Elisabet Fernandez, additional, Burford, Anna, additional, Molinari, Valeria, additional, Bjerke, Lynn, additional, Grabovska, Yura, additional, Rogers, Rebecca, additional, Crampsie, Shauna, additional, Das, Molina, additional, Robinson, Simon, additional, Clarke, Matthew, additional, and Jones, Chris, additional

Published
2022
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28. DIPG-46. Radiation induced senescence in diffuse intrinsic pontine glioma cells reveals selective vulnerability to Bcl-XL inhibition

Author

Vardon, Ashley, primary, Guiho, Romain, additional, Carvalho, Diana, additional, Boult, Jessica, additional, Carter, Rebecca, additional, Grabovska, Yura, additional, Mackay, Alan, additional, Zheng, Guangrong, additional, Zhou, Daohong, additional, Hiley, Crispin, additional, Lythgoe, Mark, additional, Jones, Chris, additional, Hargrave, Darren, additional, and Martinez-, Juan-Pedro, additional

Published
2022
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30. ATRT-20. Novel prognostic molecular signatures for improved risk-classification of Atypical Teratoid Rhabdoid Tumours

Author

Keeling, Claire, primary, Grabovska, Yura, additional, O'Hare, Patricia, additional, Crosier, Stephen, additional, Pickles, Jessica C, additional, Finetti, Martina A, additional, Fairchild, Amy R, additional, Anderson, John, additional, Hargrave, Darren, additional, Brennan, Bernadette, additional, Jacques, Thomas S, additional, Clifford, Steven C, additional, Bailey, Simon, additional, and Williamson, Daniel, additional

Published
2022
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31. DIPG Harbors Alterations Targetable by MEK Inhibitors, with Acquired Resistance Mechanisms Overcome by Combinatorial Inhibition

Author

Izquierdo, Elisa, primary, Carvalho, Diana M., additional, Mackay, Alan, additional, Temelso, Sara, additional, Boult, Jessica K.R., additional, Pericoli, Giulia, additional, Fernandez, Elisabet, additional, Das, Molina, additional, Molinari, Valeria, additional, Grabovska, Yura, additional, Rogers, Rebecca F., additional, Ajmone-Cat, Maria Antonietta, additional, Proszek, Paula Z., additional, Stubbs, Mark, additional, Depani, Sarita, additional, O'Hare, Patricia, additional, Yu, Lu, additional, Roumelioti, Georgia, additional, Choudhary, Jyoti S., additional, Clarke, Matthew, additional, Fairchild, Amy R., additional, Jacques, Thomas S., additional, Grundy, Richard G., additional, Howell, Lisa, additional, Picton, Susan, additional, Adamski, Jenny, additional, Wilson, Shaun, additional, Gray, Juliet C., additional, Zebian, Bassel, additional, Marshall, Lynley V., additional, Carceller, Fernando, additional, Grill, Jacques, additional, Vinci, Maria, additional, Robinson, Simon P., additional, Hubank, Michael, additional, Hargrave, Darren, additional, and Jones, Chris, additional

Published
2022
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32. EARLY GABAERGIC NEURONAL LINEAGE DEFINES DEPENDENCIES IN HISTONE H3 G34R/V GLIOMA

Author

Liu, Ilon, Bjerke, Lynn, Cruzeiro, Gustavo Alencastro Veiga, Rogers, Rebecca F., Grabovska, Yura, Panditharatna, Eshini, Mackay, Alan, Barron, Tara, Shaw, McKenzie, Hoffman, Samantha E., Hack, Olivia A., Quezada, Michael A., Dempster, Joshua, Temelso, Sara, Englinger, Bernhard, Molinari, Valeria, Mire, Hafsa M., Jiang, Li, Madlener, Sibylle, Mayr, Lisa, Dorfer, Christian, Geyeregger, Rene, Rota, Christopher, Ricken, Gerda, Alexandrescu, Sanda, Braun, Emelie, Danan-Gotthold, Miri, Hu, Lijuan, Siletti, Kimberly, Sundstroem, Erik, Hodge, Rebecca, Lein, Ed, Agnihotri, Sameer, Eisenstat, David D., Carceller, Fernando, Stapleton, Simon, Bleil, Cristina, Mastronuzzi, Angela, Cole, Kristina A., Waanders, Angela J., Carcaboso AM, Vinci, Maria, Hargrave, Darren, Haberler, Christine, Gojo, Johannes, Slavc, Irene, Linnarsson, Sten, Monje, Michelle, Jones, Chris, and Filbin, Mariella G.

Published
2021

33. Loss of the H4 lysine methyltransferase KMT5B drives tumorigenic phenotypes by depleting H3K27me3 at loci otherwise retained in H3K27M mutant DIPG cells

Author

Kessler, Ketty, primary, Mackay, Alan, additional, Grabovska, Yura, additional, Molinari, Valeria, additional, Burford, Anna, additional, Temelso, Sara, additional, Tari, Haider, additional, Yara-Romero, Erika, additional, Liu, Ilon, additional, Yu, Lu, additional, Castel, David, additional, Choudhary, Jyoti, additional, Sottoriva, Andrea, additional, Filbin, Mariella, additional, Vinci, Mara, additional, and Jones, Chris, additional

Published
2021
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35. HGG-06. EARLY GABAERGIC NEURONAL LINEAGE DEFINES DEPENDENCIES IN HISTONE H3 G34R/V GLIOMA

Author

Liu, Ilon, primary, Bjerke, Lynn, additional, Cruzeiro, Gustavo Alencastro Veiga, additional, Rogers, Rebecca F, additional, Grabovska, Yura, additional, Panditharatna, Eshini, additional, Mackay, Alan, additional, Barron, Tara, additional, Shaw, McKenzie, additional, Hoffman, Samantha E, additional, Hack, Olivia A, additional, Quezada, Michael A, additional, Dempster, Joshua, additional, Temelso, Sara, additional, Englinger, Bernhard, additional, Molinari, Valeria, additional, Mire, Hafsa M, additional, Jiang, Li, additional, Madlener, Sibylle, additional, Mayr, Lisa, additional, Dorfer, Christian, additional, Geyeregger, Rene, additional, Rota, Christopher, additional, Ricken, Gerda, additional, Alexandrescu, Sanda, additional, Braun, Emelie, additional, Danan-Gotthold, Miri, additional, Hu, Lijuan, additional, Siletti, Kimberly, additional, Sundstroem, Erik, additional, Hodge, Rebecca, additional, Lein, Ed, additional, Agnihotri, Sameer, additional, Eisenstat, David D, additional, Carceller, Fernando, additional, Stapleton, Simon, additional, Bleil, Cristina, additional, Mastronuzzi, Angela, additional, Cole, Kristina A, additional, Waanders, Angela J, additional, Carcaboso, Angel Montero, additional, Vinci, Maria, additional, Hargrave, Darren, additional, Haberler, Christine, additional, Gojo, Johannes, additional, Slavc, Irene, additional, Linnarsson, Sten, additional, Monje, Michelle, additional, Jones, Chris, additional, and Filbin, Mariella G, additional

Published
2021
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36. Drug screening linked to molecular profiling identifies novel dependencies in patient-derived primary cultures of paediatric high grade glioma and DIPG

Author

Carvalho, Diana M, primary, Temelso, Sara, additional, Mackay, Alan, additional, Pemberton, Helen N, additional, Rogers, Rebecca, additional, Kessler, Ketty, additional, Izquierdo, Elisa, additional, Bjerke, Lynn, additional, Salom, Janat Fazal, additional, Clarke, Matthew, additional, Grabovska, Yura, additional, Burford, Anna, additional, Olaciregui, Nagore Gene, additional, Boult, Jessica KR, additional, Molinari, Valeria, additional, Fofana, Mariama, additional, Proszek, Paula, additional, Potente, Elisabet F, additional, Taylor, Kathryn R, additional, Chandler, Christopher, additional, Zebian, Bassel, additional, Bhangoo, Ranj, additional, Martin, Andrew J, additional, Dabbous, Bassam, additional, Stapleton, Simon, additional, Hettige, Samantha, additional, Marshall, Lynley V, additional, Carceller, Fernando, additional, Mandeville, Henry C, additional, Vaidya, Sucheta J, additional, Al-Sarraj, Safa, additional, Bridges, Leslie R, additional, Johnston, Robert, additional, Cryan, Jane, additional, Farrell, Michael, additional, Crimmins, Darach, additional, Caird, John, additional, Pears, Jane, additional, Pericoli, Giulia, additional, Miele, Evelina, additional, Mastronuzzi, Angela, additional, Locatelli, Franco, additional, Carai, Andrea, additional, Robinson, Simon P, additional, Hubank, Mike, additional, Monje, Michelle, additional, Moore, Andrew S, additional, Hassall, Timothy EG, additional, Carcaboso, Angel Montero, additional, Lord, Christopher J, additional, Vinci, Mara, additional, and Jones, Chris, additional

Published
2020
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37. Platelet-derived growth factor beta is a potent inflammatory driver in paediatric high-grade glioma

Author

Ross, James L, primary, Chen, Zhihong, additional, Herting, Cameron J, additional, Grabovska, Yura, additional, Szulzewsky, Frank, additional, Puigdelloses, Montserrat, additional, Monterroza, Lenore, additional, Switchenko, Jeffrey, additional, Wadhwani, Nitin R, additional, Cimino, Patrick J, additional, Mackay, Alan, additional, Jones, Chris, additional, Read, Renee D, additional, MacDonald, Tobey J, additional, Schniederjan, Matthew, additional, Becher, Oren J, additional, and Hambardzumyan, Dolores, additional

Published
2020
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38. Corrigendum to: Molecular subgrouping of atypical teratoid/rhabdoid tumors—a reinvestigation and current consensus

Author

Ho, Ben, primary, Johann, Pascal D, additional, Grabovska, Yura, additional, De Dieu Andrianteranagna, Mamy Jean, additional, Yao, Fu Pan, additional, Frühwald, Michael, additional, Hasselblatt, Martin, additional, Bourdeaut, Franck, additional, Williamson, Daniel, additional, Huang, Annie, additional, and Kool, Marcel, additional

Published
2020
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39. MBRS-44. TIME, PATTERN AND OUTCOME OF MEDULLOBLASTOMA RELAPSE ARE ASSOCIATED WITH TUMOUR BIOLOGY AT DIAGNOSIS AND UPFRONT THERAPY: A COHORT STUDY

Author

Hill, Rebecca, primary, Richardson, Stacey, additional, Schwalbe, Edward, additional, Hicks, Debbie, additional, Lindsey, Janet, additional, Crosier, Stephen, additional, Rafiee, Gholamreza, additional, Grabovska, Yura, additional, Wharton, Stephen, additional, Jacques, Thomas, additional, Michalski, Anthony, additional, Joshi, Abhijit, additional, Pizer, Barry, additional, Williamson, Daniel, additional, Bailey, Simon, additional, and Clifford, Steven, additional

Published
2020
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40. MBRS-60. THE ACTIONABLE GENOMIC LANDSCAPE OF RELAPSED MEDULLOBLASTOMA IS DEFINED BY MAINTENANCE AND ACQUISITION OF DRIVER EVENTS

Author

Richardson, Stacey, primary, Hill, Rebecca M, additional, Kui, Christopher, additional, Lindsey, Janet C, additional, Grabovska, Yura, additional, Schwalbe, Edward C, additional, Hicks, Debbie, additional, Williamson, Daniel, additional, Crosier, Stephen, additional, Joshi, Abjhit, additional, Wharton, Stephen B, additional, Hansford, Jordan, additional, Pizer, Barry, additional, Vinci, Maria, additional, Mastronuzzi, Angela, additional, Carai, Andrea, additional, Michalski, Anthony, additional, Jacques, Thomas S, additional, Bailey, Simon, additional, and Clifford, Steven C, additional

Published
2020
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41. HGG-37. PAEDIATRIC GLIOBLASTOMA CELLS SHOW CRITICAL DEPENDENCIES ON EPIGENOMIC AND EPITRANSCRIPTOMIC CONTROL OF GENE EXPRESSION BY H3.3G34R/V MUTATIONS

Author

Bjerke, Lynn, primary, Mackay, Alan, additional, Rogers, Rebecca, additional, Grabovska, Yura, additional, Molinari, Valeria, additional, Temelso, Sara, additional, Cole, Kristina, additional, Waanders, Angela, additional, Carcaboso, Angel Montero, additional, Vinci, Maria, additional, and Jones, Chris, additional

Published
2020
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42. Time, pattern, and outcome of medulloblastoma relapse and their association with tumour biology at diagnosis and therapy: a multicentre cohort study

Author

Hill, Rebecca M, primary, Richardson, Stacey, additional, Schwalbe, Edward C, additional, Hicks, Debbie, additional, Lindsey, Janet C, additional, Crosier, Stephen, additional, Rafiee, Gholamreza, additional, Grabovska, Yura, additional, Wharton, Stephen B, additional, Jacques, Thomas S, additional, Michalski, Antony, additional, Joshi, Abhijit, additional, Pizer, Barry, additional, Williamson, Daniel, additional, Bailey, Simon, additional, and Clifford, Steven C, additional

Published
2020
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44. PATH-23. GENOMIC LANDSCAPE OF IDH-MUTANT PRIMARY GLIOBLASTOMAS SHOWS DISTINCT CLINICAL AND MOLECULAR FEATURES AND THAT CDKN2A SHOULD BE SUPPLEMENTED WITH MGMTp AND G-CIMP FOR PRECISE PROGNOSTICATION

Author

Wong, Queenie Hoi-Wing, primary, Wong, Gabriel Chun-Hei, additional, Chan, Aden Ka-Yin, additional, Poon, Wai Sang, additional, Chan, Danny Tat-Ming, additional, Chen, Hong, additional, Zhang, Zhen-yu, additional, Noushmehr, Houtan, additional, Jones, Chris, additional, Grabovska, Yura, additional, Mackay, Alan, additional, Chow, Chit, additional, Kwan, Johnny Sheung Him, additional, Chung, Nellie Yuk-Fei, additional, Huang, Queenie Junqi, additional, Poon, Manix Fung-Man, additional, Shi, Zhi-feng, additional, Li, Kay Ka-Wai, additional, and Ng, Ho-Keung, additional

Published
2020
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45. DDRE-07. DIPG HARBOUR ALTERATIONS TARGETABLE BY MEK INHIBITORS, WITH ACQUIRED RESISTANCE MECHANISMS OVERCOME BY COMBINATORIAL INHIBITION

Author

Izquierdo, Elisa, primary, Carvalho, Diana, additional, Mackay, Alan, additional, Temelso, Sara, additional, Boult, Jessica K R, additional, Molinari, Valeria, additional, Stubbs, Mark, additional, Grabovska, Yura, additional, Yu, Lu, additional, Choudhary, Jyoti, additional, Depani, Sarita, additional, o’Hare, Patricia, additional, Robinson, Simon P, additional, Hubank, Michael, additional, Hargrave, Darren, additional, and Jones, Chris, additional

Published
2020
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46. DNA methylation-based profiling for paediatric CNS tumour diagnosis and treatment: a population-based study

Author

Pickles, Jessica C, primary, Fairchild, Amy R, additional, Stone, Thomas J, additional, Brownlee, Lorelle, additional, Merve, Ashirwad, additional, Yasin, Shireena A, additional, Avery, Aimee, additional, Ahmed, Saira W, additional, Ogunbiyi, Olumide, additional, Gonzalez Zapata, Jamie, additional, Peary, Abigail F, additional, Edwards, Marie, additional, Wilkhu, Lisa, additional, Dryden, Carryl, additional, Ladon, Dariusz, additional, Kristiansen, Mark, additional, Rowe, Catherine, additional, Kurian, Kathreena M, additional, Nicoll, James A R, additional, Mitchell, Clare, additional, Bloom, Tabitha, additional, Hilton, David A, additional, Al-Sarraj, Safa, additional, Doey, Lawrence, additional, Johns, Paul N, additional, Bridges, Leslie R, additional, Chakrabarty, Aruna, additional, Ismail, Azzam, additional, Rathi, Nitika, additional, Syed, Khaja, additional, Lammie, G Alistair, additional, Limback-Stanic, Clara, additional, Smith, Colin, additional, Torgersen, Antonia, additional, Rae, Frances, additional, Hill, Rebecca M, additional, Clifford, Steven C, additional, Grabovska, Yura, additional, Williamson, Daniel, additional, Clarke, Matthew, additional, Jones, Chris, additional, Capper, David, additional, Sill, Martin, additional, von Deimling, Andreas, additional, Pfister, Stefan M, additional, Jones, David T W, additional, Hargrave, Darren, additional, Chalker, Jane, additional, and Jacques, Thomas S, additional

Published
2020
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48. Platelet-derived growth factor beta is a potent inflammatory driver in paediatric high-grade glioma.

Author

Ross, James L, Chen, Zhihong, Herting, Cameron J, Grabovska, Yura, Szulzewsky, Frank, Puigdelloses, Montserrat, Monterroza, Lenore, Switchenko, Jeffrey, Wadhwani, Nitin R, Cimino, Patrick J, Mackay, Alan, Jones, Chris, Read, Renee D, MacDonald, Tobey J, Schniederjan, Matthew, Becher, Oren J, and Hambardzumyan, Dolores

Subjects
PLATELET-derived growth factor, GLIOMAS, GENE expression profiling, CEREBELLAR tumors, KNOCKOUT mice, BRAIN death, RESEARCH funding
Abstract

Paediatric high-grade gliomas (HGGs) account for the most brain tumour-related deaths in children and have a median survival of 12-15 months. One promising avenue of research is the development of novel therapies targeting the properties of non-neoplastic cell-types within the tumour such as tumour associated macrophages (TAMs). TAMs are immunosuppressive and promote tumour malignancy in adult HGG; however, in paediatric medulloblastoma, TAMs exhibit anti-tumour properties. Much is known about TAMs in adult HGG, yet little is known about them in the paediatric setting. This raises the question of whether paediatric HGGs possess a distinct constituency of TAMs because of their unique genetic landscapes. Using human paediatric HGG tissue samples and murine models of paediatric HGG, we demonstrate diffuse midline gliomas possess a greater inflammatory gene expression profile compared to hemispheric paediatric HGGs. We also show despite possessing sparse T-cell infiltration, human paediatric HGGs possess high infiltration of IBA1+ TAMs. CD31, PDGFRβ, and PDGFB all strongly correlate with IBA1+ TAM infiltration. To investigate the TAM population, we used the RCAS/tv-a system to recapitulate paediatric HGG in newborn immunocompetent mice. Tumours are induced in Nestin-positive brain cells by PDGFA or PDGFB overexpression with Cdkn2a or Tp53 co-mutations. Tumours driven by PDGFB have a significantly lower median survival compared to PDGFA-driven tumours and have increased TAM infiltration. NanoString and quantitative PCR analysis indicates PDGFB-driven tumours have a highly inflammatory microenvironment characterized by high chemokine expression. In vitro bone marrow-derived monocyte and microglial cultures demonstrate bone marrow-derived monocytes are most responsible for the production of inflammatory signals in the tumour microenvironment in response to PDGFB stimulation. Lastly, using knockout mice deficient for individual chemokines, we demonstrate the feasibility of reducing TAM infiltration and prolonging survival in both PDGFA and PDGFB-driven tumours. We identify CCL3 as a potential key chemokine in these processes in both humans and mice. Together, these studies provide evidence for the potent inflammatory effects PDGFB has in paediatric HGGs. [ABSTRACT FROM AUTHOR]

Published
2021
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