Search

Your search keyword '"Hill, Rebecca M."' showing total 158 results
Start Over Author "Hill, Rebecca M."
158 results on '"Hill, Rebecca M."'

2. Molecular characterisation defines clinically-actionable heterogeneity within Group 4 medulloblastoma and improves disease risk-stratification

Author

Goddard, Jack, Castle, Jemma, Southworth, Emily, Fletcher, Anya, Crosier, Stephen, Martin-Guerrero, Idoia, García-Ariza, Miguel, Navajas, Aurora, Masliah-Planchon, Julien, Bourdeaut, Franck, Dufour, Christelle, Ayrault, Olivier, Goschzik, Tobias, Pietsch, Torsten, Sill, Martin, Pfister, Stefan M., Rutkowski, Stefan, Richardson, Stacey, Hill, Rebecca M., Williamson, Daniel, Bailey, Simon, Schwalbe, Edward C., Clifford, Steven C., and Hicks, Debbie

Published
2023
Full Text
View/download PDF

5. Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma.

Author

Zhukova, Nataliya, Ramaswamy, Vijay, Remke, Marc, Pfaff, Elke, Shih, David JH, Martin, Dianna C, Castelo-Branco, Pedro, Baskin, Berivan, Ray, Peter N, Bouffet, Eric, von Bueren, André O, Jones, David TW, Northcott, Paul A, Kool, Marcel, Sturm, Dominik, Pugh, Trevor J, Pomeroy, Scott L, Cho, Yoon-Jae, Pietsch, Torsten, Gessi, Marco, Rutkowski, Stefan, Bognar, Laszlo, Klekner, Almos, Cho, Byung-Kyu, Kim, Seung-Ki, Wang, Kyu-Chang, Eberhart, Charles G, Fevre-Montange, Michelle, Fouladi, Maryam, French, Pim J, Kros, Max, Grajkowska, Wieslawa A, Gupta, Nalin, Weiss, William A, Hauser, Peter, Jabado, Nada, Jouvet, Anne, Jung, Shin, Kumabe, Toshihiro, Lach, Boleslaw, Leonard, Jeffrey R, Rubin, Joshua B, Liau, Linda M, Massimi, Luca, Pollack, Ian F, Shin Ra, Young, Van Meir, Erwin G, Zitterbart, Karel, Schüller, Ulrich, Hill, Rebecca M, Lindsey, Janet C, Schwalbe, Ed C, Bailey, Simon, Ellison, David W, Hawkins, Cynthia, Malkin, David, Clifford, Steven C, Korshunov, Andrey, Pfister, Stefan, Taylor, Michael D, and Tabori, Uri

Subjects
Humans, Medulloblastoma, Cerebellar Neoplasms, Prognosis, Gene Expression Profiling, Mutation, Genes, p53, Adolescent, Adult, Middle Aged, Child, Child, Preschool, Infant, Female, Male, Young Adult, Brain Disorders, Pediatric Cancer, Pediatric, Rare Diseases, Brain Cancer, Genetics, Cancer, Neurosciences, Clinical Sciences, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposeReports detailing the prognostic impact of TP53 mutations in medulloblastoma offer conflicting conclusions. We resolve this issue through the inclusion of molecular subgroup profiles.Patients and methodsWe determined subgroup affiliation, TP53 mutation status, and clinical outcome in a discovery cohort of 397 medulloblastomas. We subsequently validated our results on an independent cohort of 156 medulloblastomas.ResultsTP53 mutations are enriched in wingless (WNT; 16%) and sonic hedgehog (SHH; 21%) medulloblastomas and are virtually absent in subgroups 3 and 4 tumors (P < .001). Patients with SHH/TP53 mutant tumors are almost exclusively between ages 5 and 18 years, dramatically different from the general SHH distribution (P < .001). Children with SHH/TP53 mutant tumors harbor 56% germline TP53 mutations, which are not observed in children with WNT/TP53 mutant tumors. Five-year overall survival (OS; ± SE) was 41% ± 9% and 81% ± 5% for patients with SHH medulloblastomas with and without TP53 mutations, respectively (P < .001). Furthermore, TP53 mutations accounted for 72% of deaths in children older than 5 years with SHH medulloblastomas. In contrast, 5-year OS rates were 90% ± 9% and 97% ± 3% for patients with WNT tumors with and without TP53 mutations (P = .21). Multivariate analysis revealed that TP53 status was the most important risk factor for SHH medulloblastoma. Survival rates in the validation cohort mimicked the discovery results, revealing that poor survival of TP53 mutations is restricted to patients with SHH medulloblastomas (P = .012) and not WNT tumors.ConclusionSubgroup-specific analysis reconciles prior conflicting publications and confirms that TP53 mutations are enriched among SHH medulloblastomas, in which they portend poor outcome and account for a large proportion of treatment failures in these patients.

Published
2013

6. Second-generation molecular subgrouping of medulloblastoma: an international meta-analysis of Group 3 and Group 4 subtypes

Author

Sharma, Tanvi, Schwalbe, Edward C., Williamson, Daniel, Sill, Martin, Hovestadt, Volker, Mynarek, Martin, Rutkowski, Stefan, Robinson, Giles W., Gajjar, Amar, Cavalli, Florence, Ramaswamy, Vijay, Taylor, Michael D., Lindsey, Janet C., Hill, Rebecca M., Jäger, Natalie, Korshunov, Andrey, Hicks, Debbie, Bailey, Simon, Kool, Marcel, Chavez, Lukas, Northcott, Paul A., Pfister, Stefan M., and Clifford, Steven C.

Published
2019
Full Text
View/download PDF

8. Methylphenidate improves cognitive function and health-related quality of life in survivors of childhood brain tumours.

Author

Verity, Sarah J., Halliday, Gail, Hill, Rebecca M., Ryles, Jade, and Bailey, Simon

Subjects
QUALITY of life, BRAIN tumors, COGNITIVE ability, METHYLPHENIDATE, COGNITIVE processing speed, AUDITORY perception
Abstract

Objectives: The growing population of survivors of childhood brain tumors present the challenge of long-term quality of survival. The domains most affected by tumor and treatment are those implicated in development of typical intellectual functions: attention, working memory, and processing speed, with consequent effects upon function and quality of life. In this paper we present service evaluation data on the 12-month effect upon processing speed, visual and auditory attentional domains in 29 patients receiving methylphenidate aged 5-16 years (Mean=10.6). Methods: Patients received immediate-release methylphenidate and were converted to modified-release as appropriate. Mean optimal dose of immediate-release methylphenidate was 0.34 mg/kg per dose (range 0.2-0.67). Results: Patients showed a significant positive impact of methylphenidate on attention in all tests of selective visual attention from the Test of Everyday Attention for Children 2. A significant improvement was also shown on response time. Significant change was not found on psychometric measures of sustained auditory or visual attention, or selective auditory attention. Ratings of Health-Related Quality of Life showed a positive benefit of methylphenidate at 12 months. Side effects were minimal and not statistically significant. Conclusions: Survivors of childhood brain tumor with attentional and processing speed deficit show clinical benefit from methylphenidate. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

9. Supplementary Table S3 from Dormant SOX9-Positive Cells Facilitate MYC-Driven Recurrence of Medulloblastoma

Author

Borgenvik, Anna, primary, Holmberg, Karl O., primary, Bolin, Sara, primary, Zhao, Miao, primary, Savov, Vasil, primary, Rosén, Gabriela, primary, Hutter, Sonja, primary, Garancher, Alexandra, primary, Rahmanto, Aldwin Suryo, primary, Bergström, Tobias, primary, Olsen, Thale Kristin, primary, Mainwaring, Oliver J., primary, Sattanino, Damiana, primary, Verbaan, Annemieke D., primary, Rusert, Jessica M., primary, Sundström, Anders, primary, Bravo, Mar Ballester, primary, Dang, Yonglong, primary, Wenz, Amelie S., primary, Richardson, Stacey, primary, Fotaki, Grammatiki, primary, Hill, Rebecca M., primary, Dubuc, Adrian M., primary, Kalushkova, Antonia, primary, Remke, Marc, primary, Čančer, Matko, primary, Jernberg-Wiklund, Helena, primary, Giraud, Géraldine, primary, Chen, Xingqi, primary, Taylor, Michael D., primary, Sangfelt, Olle, primary, Clifford, Steven C., primary, Schüller, Ulrich, primary, Wechsler-Reya, Robert J., primary, Weishaupt, Holger, primary, and Swartling, Fredrik J., primary

Published
2023
Full Text
View/download PDF

10. Supplementary Data from Dormant SOX9-Positive Cells Facilitate MYC-Driven Recurrence of Medulloblastoma

Author

Borgenvik, Anna, primary, Holmberg, Karl O., primary, Bolin, Sara, primary, Zhao, Miao, primary, Savov, Vasil, primary, Rosén, Gabriela, primary, Hutter, Sonja, primary, Garancher, Alexandra, primary, Rahmanto, Aldwin Suryo, primary, Bergström, Tobias, primary, Olsen, Thale Kristin, primary, Mainwaring, Oliver J., primary, Sattanino, Damiana, primary, Verbaan, Annemieke D., primary, Rusert, Jessica M., primary, Sundström, Anders, primary, Bravo, Mar Ballester, primary, Dang, Yonglong, primary, Wenz, Amelie S., primary, Richardson, Stacey, primary, Fotaki, Grammatiki, primary, Hill, Rebecca M., primary, Dubuc, Adrian M., primary, Kalushkova, Antonia, primary, Remke, Marc, primary, Čančer, Matko, primary, Jernberg-Wiklund, Helena, primary, Giraud, Géraldine, primary, Chen, Xingqi, primary, Taylor, Michael D., primary, Sangfelt, Olle, primary, Clifford, Steven C., primary, Schüller, Ulrich, primary, Wechsler-Reya, Robert J., primary, Weishaupt, Holger, primary, and Swartling, Fredrik J., primary

Published
2023
Full Text
View/download PDF

11. Supplementary Figure Legends from Dormant SOX9-Positive Cells Facilitate MYC-Driven Recurrence of Medulloblastoma

Author

Borgenvik, Anna, primary, Holmberg, Karl O., primary, Bolin, Sara, primary, Zhao, Miao, primary, Savov, Vasil, primary, Rosén, Gabriela, primary, Hutter, Sonja, primary, Garancher, Alexandra, primary, Rahmanto, Aldwin Suryo, primary, Bergström, Tobias, primary, Olsen, Thale Kristin, primary, Mainwaring, Oliver J., primary, Sattanino, Damiana, primary, Verbaan, Annemieke D., primary, Rusert, Jessica M., primary, Sundström, Anders, primary, Bravo, Mar Ballester, primary, Dang, Yonglong, primary, Wenz, Amelie S., primary, Richardson, Stacey, primary, Fotaki, Grammatiki, primary, Hill, Rebecca M., primary, Dubuc, Adrian M., primary, Kalushkova, Antonia, primary, Remke, Marc, primary, Čančer, Matko, primary, Jernberg-Wiklund, Helena, primary, Giraud, Géraldine, primary, Chen, Xingqi, primary, Taylor, Michael D., primary, Sangfelt, Olle, primary, Clifford, Steven C., primary, Schüller, Ulrich, primary, Wechsler-Reya, Robert J., primary, Weishaupt, Holger, primary, and Swartling, Fredrik J., primary

Published
2023
Full Text
View/download PDF

12. ARF suppression by MYC but not MYCN confers increased malignancy of aggressive pediatric brain tumors

Author

Mainwaring, Oliver, Weishaupt, Holger, Zhao, Miao, Rosén, Gabriela, Borgenvik, Anna, Breinschmid, Laura, Verbaan, Annemieke D., Richardson, Stacey, Thompson, Dean, Clifford, Steven C., Hill, Rebecca M., Annusver, Karl, Sundström, Anders, Holmberg Olausson, Karl, Kasper, Maria, Hutter, Sonja, Swartling, Fredrik J., Mainwaring, Oliver, Weishaupt, Holger, Zhao, Miao, Rosén, Gabriela, Borgenvik, Anna, Breinschmid, Laura, Verbaan, Annemieke D., Richardson, Stacey, Thompson, Dean, Clifford, Steven C., Hill, Rebecca M., Annusver, Karl, Sundström, Anders, Holmberg Olausson, Karl, Kasper, Maria, Hutter, Sonja, and Swartling, Fredrik J.

Abstract

Medulloblastoma, the most common malignant pediatric brain tumor, often harbors MYC amplifications. Compared to high-grade gliomas, MYC-amplified medulloblastomas often show increased photoreceptor activity and arise in the presence of a functional ARF/p53 suppressor pathway. Here, we generate an immunocompetent transgenic mouse model with regulatable MYC that develop clonal tumors that molecularly resemble photoreceptor-positive Group 3 medulloblastoma. Compared to MYCN-expressing brain tumors driven from the same promoter, pronounced ARF silencing is present in our MYC-expressing model and in human medulloblastoma. While partial Arf suppression causes increased malignancy in MYCN-expressing tumors, complete Arf depletion promotes photoreceptor-negative high-grade glioma formation. Computational models and clinical data further identify drugs targeting MYC-driven tumors with a suppressed but functional ARF pathway. We show that the HSP90 inhibitor, Onalespib, significantly targets MYC-driven but not MYCN-driven tumors in an ARF-dependent manner. The treatment increases cell death in synergy with cisplatin and demonstrates potential for targeting MYC-driven medulloblastoma., De två första författarna delar förstaförfattarskapet.

Published
2023
Full Text
View/download PDF

13. Molecular characterisation defines clinically-actionable heterogeneity within Group 4 medulloblastoma and improves disease risk-stratification

Author

Genética, antropología física y fisiología animal, Genetika,antropologia fisikoa eta animalien fisiologia, Goddard, Jack, Castle, Jemma, Southworth, Emily, Fletcher, Anya, Crosier, Stephen, Martín Guerrero, Idoia, García Ariza, Miguel, Navajas Gutiérrez, Aurora, Masliah-Planchon, Julien, Bourdeaut, Franck, Dufour, Christelle, Ayrault, Olivier, Goschzik, Tobias, Pietsch, Torsten, Sill, Martin, Pfister, Stefan M, Rutkowski, Stefan, Richardson, Stacey, Hill, Rebecca M, Williamson, Daniel, Bailey, Simon, Schwalbe, Edward C, Clifford, Steven, Hicks, Debbie, Genética, antropología física y fisiología animal, Genetika,antropologia fisikoa eta animalien fisiologia, Goddard, Jack, Castle, Jemma, Southworth, Emily, Fletcher, Anya, Crosier, Stephen, Martín Guerrero, Idoia, García Ariza, Miguel, Navajas Gutiérrez, Aurora, Masliah-Planchon, Julien, Bourdeaut, Franck, Dufour, Christelle, Ayrault, Olivier, Goschzik, Tobias, Pietsch, Torsten, Sill, Martin, Pfister, Stefan M, Rutkowski, Stefan, Richardson, Stacey, Hill, Rebecca M, Williamson, Daniel, Bailey, Simon, Schwalbe, Edward C, Clifford, Steven, and Hicks, Debbie

Abstract

Group 4 tumours (MBGrp4) represent the majority of non-WNT/non-SHH medulloblastomas. Their clinical course is poorly predicted by current risk-factors. MBGrp4 molecular substructures have been identified (e.g. subgroups/cytogenetics/mutations), however their inter-relationships and potential to improve clinical sub-classification and risk-stratification remain undefined. We comprehensively characterised the paediatric MBGrp4 molecular landscape and determined its utility to improve clinical management. A clinically-annotated discovery cohort (n = 362 MBGrp4) was assembled from UK-CCLG institutions and SIOP-UKCCSG-PNET3, HIT-SIOP-PNET4 and PNET HR + 5 clinical trials. Molecular profiling was undertaken, integrating driver mutations, second-generation non-WNT/non-SHH subgroups (1-8) and whole-chromosome aberrations (WCAs). Survival models were derived for patients ≥ 3 years of age who received contemporary multi-modal therapies (n = 323). We first independently derived and validated a favourable-risk WCA group (WCA-FR) characterised by ≥ 2 features from chromosome 7 gain, 8 loss, and 11 loss. Remaining patients were high-risk (WCA-HR). Subgroups 6 and 7 were enriched for WCA-FR (p < 0·0001) and aneuploidy. Subgroup 8 was defined by predominantly balanced genomes with isolated isochromosome 17q (p < 0·0001). While no mutations were associated with outcome and overall mutational burden was low, WCA-HR harboured recurrent chromatin remodelling mutations (p = 0·007). Integration of methylation and WCA groups improved risk-stratification models and outperformed established prognostication schemes. Our MBGrp4 risk-stratification scheme defines: favourable-risk (non-metastatic disease and (i) subgroup 7 or (ii) WCA-FR (21% of patients, 5-year PFS 97%)), very-high-risk (metastatic disease with WCA-HR (36%, 5-year PFS 49%)) and high-risk (remaining patients; 43%, 5-year PFS 67%). These findings validated in an independent MBGrp4 cohort (n = 668). Importantly, our findings demo

Published
2023

15. Dormant SOX9-Positive Cells Facilitate MYC-Driven Recurrence of Medulloblastoma

Author

Borgenvik, Anna, primary, Holmberg, Karl O., additional, Bolin, Sara, additional, Zhao, Miao, additional, Savov, Vasil, additional, Rosén, Gabriela, additional, Hutter, Sonja, additional, Garancher, Alexandra, additional, Rahmanto, Aldwin Suryo, additional, Bergström, Tobias, additional, Olsen, Thale Kristin, additional, Mainwaring, Oliver J., additional, Sattanino, Damiana, additional, Verbaan, Annemieke D., additional, Rusert, Jessica M., additional, Sundström, Anders, additional, Bravo, Mar Ballester, additional, Dang, Yonglong, additional, Wenz, Amelie S., additional, Richardson, Stacey, additional, Fotaki, Grammatiki, additional, Hill, Rebecca M., additional, Dubuc, Adrian M., additional, Kalushkova, Antonia, additional, Remke, Marc, additional, Čančer, Matko, additional, Jernberg-Wiklund, Helena, additional, Giraud, Géraldine, additional, Chen, Xingqi, additional, Taylor, Michael D., additional, Sangfelt, Olle, additional, Clifford, Steven C., additional, Schüller, Ulrich, additional, Wechsler-Reya, Robert J., additional, Weishaupt, Holger, additional, and Swartling, Fredrik J., additional

Published
2022
Full Text
View/download PDF

16. 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
Full Text
View/download PDF

18. MEDB-79. MYC-driven upregulation of thede novo serine and glycine pathway is a novel therapeutic target for Group 3 MYC-amplified Medulloblastoma

Author

Adiamah, Magretta, primary, Lindsey, Janet C, additional, Burté, Florence, additional, Kohe, Sarah, additional, Morcavallo, Alaide, additional, Blair, Helen, additional, Hill, Rebecca M, additional, Singh, Mankaran, additional, Crosier, Stephen, additional, Zhang, Tong, additional, Maddocks, Oliver, additional, Peet, Andrew, additional, Chesler, Louis, additional, Hickson, Ian, additional, Maxwell, Ross, additional, and Clifford, Steven C, additional

Published
2022
Full Text
View/download PDF

19. MEDB-71. Molecular characterisation of group 4 medulloblastoma improves risk-stratification and its biological understanding

Author

Goddard, Jack, primary, Castle, Jemma, additional, Southworth, Emily, additional, Fletcher, Anya, additional, Crosier, Stephen, additional, Martin-Guerrero, Idoia, additional, Garcia-Ariza, Miguel, additional, Navajas, Aurora, additional, Masliah-Planchon, Julien, additional, Bourdeaut, Franck, additional, Dufour, Christelle, additional, Goschizk, Tobias, additional, Pietsch, Torsten, additional, Richardson, Stacey, additional, Hill, Rebecca M, additional, Williamson, Daniel, additional, Bailey, Simon, additional, Schwalbe, Edward C, additional, Clifford, Steven C, additional, and Hicks, Debbie, additional

Published
2022
Full Text
View/download PDF

21. MEDB-43. Development of a bioinformatics pipeline for identification of differential DNA methylation events associated with medulloblastoma relapse

Author

Kui, Christopher, primary, Richardson, Stacey, additional, Schwalbe, Edward C, additional, Thompson, Dean, additional, Keeling, Claire, additional, Strathdee, Gordon, additional, Dufour, Christelle, additional, Bailey, Simon, additional, Ramaswamy, Vijay, additional, Clifford, Steven C, additional, and Hill, Rebecca M, additional

Published
2022
Full Text
View/download PDF

22. Dormant SOX9-Positive Cells Facilitate MYC-Driven Recurrence of Medulloblastoma

Author

Borgenvik, Anna, Holmberg, Karl O., Bolin, Sara, Zhao, Miao, Savov, Vasil, Rosén, Gabriela, Hutter, Sonja, Garancher, Alexandra, Rahmanto, Aldwin Suryo, Bergström, Tobias, Olsen, Thale Kristin, Mainwaring, Oliver, Sattanino, Damiana, Verbaan, Annemieke D., Rusert, Jessica M., Sundström, Anders, Ballester Bravo, Mar, Dang, Yonglong, Wenz, Amelie S., Richardson, Stacey, Fotaki, Grammatiki, Hill, Rebecca M., Dubuc, Adrian M., Kalushkova, Antonia, Remke, Marc, Čančer, Matko, Jernberg Wiklund, Helena, Giraud, Geraldine, Chen, Xingqi, Taylor, Michael D., Sangfelt, Olle, Clifford, Steven C., Schueller, Ulrich, Wechsler-Reya, Robert J., Weishaupt, Holger, Swartling, Fredrik J., Borgenvik, Anna, Holmberg, Karl O., Bolin, Sara, Zhao, Miao, Savov, Vasil, Rosén, Gabriela, Hutter, Sonja, Garancher, Alexandra, Rahmanto, Aldwin Suryo, Bergström, Tobias, Olsen, Thale Kristin, Mainwaring, Oliver, Sattanino, Damiana, Verbaan, Annemieke D., Rusert, Jessica M., Sundström, Anders, Ballester Bravo, Mar, Dang, Yonglong, Wenz, Amelie S., Richardson, Stacey, Fotaki, Grammatiki, Hill, Rebecca M., Dubuc, Adrian M., Kalushkova, Antonia, Remke, Marc, Čančer, Matko, Jernberg Wiklund, Helena, Giraud, Geraldine, Chen, Xingqi, Taylor, Michael D., Sangfelt, Olle, Clifford, Steven C., Schueller, Ulrich, Wechsler-Reya, Robert J., Weishaupt, Holger, and Swartling, Fredrik J.

Abstract

Relapse is the leading cause of death in patients with medulloblas-toma, the most common malignant pediatric brain tumor. A better understanding of the mechanisms underlying recurrence could lead to more effective therapies for targeting tumor relapses. Here, we observed that SOX9, a transcription factor and stem cell/glial fate marker, is limited to rare, quiescent cells in high-risk medulloblastoma with MYC amplification. In paired primary-recurrent patient samples, SOX9-positive cells accumulated in medulloblastoma relapses. SOX9 expression anti-correlated with MYC expression in murine and human medulloblastoma cells. However, SOX9-positive cells were plastic and could give rise to a MYC high state. To follow relapse at the single-cell level, an inducible dual Tet model of medulloblastoma was developed, in which MYC expression was redirected in vivo from treatment-sensitive bulk cells to dormant SOX9-positive cells using doxycycline treatment. SOX9 was essential for relapse initiation and depended on suppression of MYC activity to promote therapy resistance, epithelial-mesenchymal transition, and immune escape. p53 and DNA repair pathways were downregulated in recurrent tumors, whereas MGMT was upregulated. Recurrent tumor cells were found to be sensitive to treatment with an MGMT inhibitor and doxorubicin. These findings suggest that recurrence-specific targeting coupled with DNA repair inhibition comprises a potential therapeutic strategy in patients affected by medulloblastoma relapse.Significance: SOX9 facilitates therapy escape and recurrence in medulloblastoma via temporal inhibition of MYC/MYCN genes, revealing a strategy to specifically target SOX9-positive cells to prevent tumor relapse.

Published
2022
Full Text
View/download PDF

23. Relapsed medulloblastoma in pre-irradiated patients: Current practice for diagnostics and treatment

Author

Hill, Rebecca M., Plasschaert, Sabine L.A., Timmermann, Beate, Dufour, Christelle, Aquilina, Kristian, Avula, Shivaram, Donovan, Laura, Lequin, Maarten, Pietsch, Torsten, Thomale, Ulrich, Tippelt, Stephan, Wesseling, Pieter, Rutkowski, Stefan, Clifford, Steven C., Pfister, Stefan M., Bailey, Simon, Fleischhack, Gudrun, Hill, Rebecca M., Plasschaert, Sabine L.A., Timmermann, Beate, Dufour, Christelle, Aquilina, Kristian, Avula, Shivaram, Donovan, Laura, Lequin, Maarten, Pietsch, Torsten, Thomale, Ulrich, Tippelt, Stephan, Wesseling, Pieter, Rutkowski, Stefan, Clifford, Steven C., Pfister, Stefan M., Bailey, Simon, and Fleischhack, Gudrun

Published
2022

30. Relapsed Medulloblastoma in Pre-Irradiated Patients: Current Practice for Diagnostics and Treatment

Author

Hill, Rebecca M., primary, Plasschaert, Sabine L. A., additional, Timmermann, Beate, additional, Dufour, Christelle, additional, Aquilina, Kristian, additional, Avula, Shivaram, additional, Donovan, Laura, additional, Lequin, Maarten, additional, Pietsch, Torsten, additional, Thomale, Ulrich, additional, Tippelt, Stephan, additional, Wesseling, Pieter, additional, Rutkowski, Stefan, additional, Clifford, Steven C., additional, Pfister, Stefan M., additional, Bailey, Simon, additional, and Fleischhack, Gudrun, additional

Published
2021
Full Text
View/download PDF

31. Histologically defined central nervous system primitive neuro-ectodermal tumours (CNS-PNETs) display heterogeneous DNA methylation profiles and show relationships to other paediatric brain tumour types

Author

Schwalbe, Ed. C., Hayden, James T., Rogers, Hazel A., Miller, Suzanne, Lindsey, Janet C., Hill, Rebecca M., Nicholson, Sarah-Leigh, Kilday, John-Paul, Adamowicz-Brice, Martyna, Storer, Lisa, Jacques, Thomas S., Robson, Keith, Lowe, Jim, Williamson, Daniel, Grundy, Richard G., Bailey, Simon, and Clifford, Steven C.

Published
2013
Full Text
View/download PDF

32. Emergence and maintenance of actionable genetic drivers at medulloblastoma relapse

Author

Richardson, Stacey, primary, Hill, Rebecca M, additional, Kui, Christopher, additional, Lindsey, Janet C, additional, Grabovksa, Yura, additional, Keeling, Claire, additional, Pease, Louise, additional, Bashton, Matthew, additional, Crosier, Stephen, additional, Vinci, Maria, additional, André, Nicolas, additional, Figarella-Branger, Dominique, additional, Hansford, Jordan R, additional, Lastowska, Maria, additional, Zakrzewski, Krzysztof, additional, Jorgensen, Mette, additional, Pickles, Jessica C, additional, Taylor, Michael D, additional, Pfister, Stefan M, additional, Wharton, Stephen B, additional, Pizer, Barry, additional, Michalski, Antony, additional, Joshi, Abhijit, additional, Jacques, Thomas S, additional, Hicks, Debbie, additional, Schwalbe, Edward C, additional, Williamson, Daniel, additional, Ramaswamy, Vijay, additional, Bailey, Simon, additional, and Clifford, Steven C, additional

Published
2021
Full Text
View/download PDF

33. 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
Full Text
View/download PDF

34. 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
Full Text
View/download PDF

35. MBRS-10. QUIESCENT SOX9-POSITIVE CELLS BEHIND MYC DRIVEN MEDULLOBLASTOMA RECURRENCE

Author

Bolin, Sara, primary, Savov, Vasil, additional, Borgenvik, Anna, additional, Rosén, Gabriela, additional, Olausson, Karl Holmberg, additional, Zhao, Miao, additional, Garancher, Alexandra, additional, Rahmanto, Aldwin Suryo, additional, Hutter, Sonja, additional, Mainwaring, Oliver, additional, Rusert, Jessica, additional, Sundstrom, Anders, additional, Richardson, Stacey, additional, Fotaki, Grammatiki, additional, Hill, Rebecca M, additional, Dubuc, Adrian M, additional, Kalushkova, Antonia, additional, Remke, Marc, additional, Čančer, Matko, additional, Jernberg-Wiklund, Helena, additional, Ramaswamy, Vijay, additional, Chen, Xingqi, additional, Taylor, Michael D, additional, Sangfelt, Olle, additional, Schüller, Ulrich, additional, Clifford, Steve C, additional, Wechsler-Reya, Robert J, additional, Weishaupt, Holger, additional, and Swartling, Fredrik J, additional

Published
2020
Full Text
View/download PDF

36. Abstract B73: Second-generation molecular subgrouping of medulloblastoma: An international meta-analysis of Group 3 and Group 4 subtypes

Author

Sharma, Tanvi, primary, Schwalbe, Edward C., additional, Williamson, Daniel W., additional, Sill, Martin, additional, Hovestadt, Volker, additional, Mynarek, Martin, additional, Rutkowski, Stefan, additional, Robinson, Giles W., additional, Gajjar, Amar, additional, Cavalli, Florence, additional, Ramaswamy, Vijay, additional, Taylor, Michael D., additional, Lindsey, Janet C., additional, Hill, Rebecca M., additional, Jäger, Natalie, additional, Korshunov, Andrey, additional, Hicks, Debbie, additional, Bailey, Simon, additional, Kool, Marcel, additional, Chavez, Lukas, additional, Northcott, Paul A., additional, Pfister, Stefan M., additional, and Clifford, Steven C., additional

Published
2020
Full Text
View/download PDF

37. 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
Full Text
View/download PDF

38. Emergence and maintenance of actionable genetic drivers at medulloblastoma relapse.

Author

Richardson, Stacey, Hill, Rebecca M, Kui, Christopher, Lindsey, Janet C, Grabovksa, Yura, Keeling, Claire, Pease, Louise, Bashton, Matthew, Crosier, Stephen, Vinci, Maria, André, Nicolas, Figarella-Branger, Dominique, Hansford, Jordan R, Lastowska, Maria, Zakrzewski, Krzysztof, Jorgensen, Mette, Pickles, Jessica C, Taylor, Michael D, Pfister, Stefan M, and Wharton, Stephen B

Published
2022
Full Text
View/download PDF

39. NOVEL MOLECULAR SUBGROUPS FOR CLINICAL CLASSIFICATION AND OUTCOME PREDICTION IN CHILDHOOD MEDULLOBLASTOMA: A COHORT STUDY

Author

Schwalbe, Edward C., Lindsey, Janet C., Nakjang, Sirintra, Crosier, Stephen, Smith, Amanda J., Hicks, Debbie, Rafiee, Gholamreza, Hill, Rebecca M., Iliasova, Alice, Bailey, S., Stone, Thomas, Pizer, Barry, Michalski, Antony, Joshi, Abhijit, Wharton, Stephen B., Jacques, Thomas S, Bailey, Simon, Williamson, Daniel, and Clifford, Steven C.

Subjects
SDG 3 - Good Health and Well-being
Abstract

Background International consensus recognises four medulloblastoma molecular subgroups: WNT (MBWNT), SHH (MBSHH), group 3 (MBGrp3), and group 4 (MBGrp4), each defined by their characteristic genome-wide transcriptomic and DNA methylomic profiles. These subgroups have distinct clinicopathological and molecular features, and underpin current disease subclassification and initial subgroup-directed therapies that are underway in clinical trials. However, substantial biological heterogeneity and differences in survival are apparent within each subgroup, which remain to be resolved. We aimed to investigate whether additional molecular subgroups exist within childhood medulloblastoma and whether these could be used to improve disease subclassification and prognosis predictions. Methods In this retrospective cohort study, we assessed 428 primary medulloblastoma samples collected from UK Children's Cancer and Leukaemia Group (CCLG) treatment centres (UK), collaborating European institutions, and the UKCCSG-SIOP-PNET3 European clinical trial. An independent validation cohort (n=276) of archival tumour samples was also analysed. We analysed samples from patients with childhood medulloblastoma who were aged 0–16 years at diagnosis, and had central review of pathology and comprehensive clinical data. We did comprehensive molecular profiling, including DNA methylation microarray analysis, and did unsupervised class discovery of test and validation cohorts to identify consensus primary molecular subgroups and characterise their clinical and biological significance. We modelled survival of patients aged 3–16 years in patients (n=215) who had craniospinal irradiation and had been treated with a curative intent. Findings Seven robust and reproducible primary molecular subgroups of childhood medulloblastoma were identified. MBWNTremained unchanged and each remaining consensus subgroup was split in two. MBSHHwas split into age-dependent subgroups corresponding to infant (

Published
2017

40. TMOD-35. CAN RARE SOX9-POSITIVE CELLS INCITE MYC-DRIVEN MEDULLOBLASTOMA RECURRENCE?

Author

Bolin, Sara, primary, Savov, Vasil, additional, Borgenvik, Anna, additional, Garancher, Alexandra, additional, Rosén, Gabriela, additional, Rahmanto, Aldwin, additional, Hutter, Sonja, additional, Rusert, Jessica, additional, Garzia, Livia, additional, Fotaki, Grammatiki, additional, Hill, Rebecca M, additional, Dubuc, Adrian M, additional, Remke, Marc, additional, aner, Matko, additional, Ramaswamy, Vijay, additional, Clifford, Steve, additional, Sangfelt, Olle, additional, Schüller, Ulrich, additional, Taylor, Michael, additional, Wechsler-Reya, Robert, additional, Weishaupt, Holger, additional, and Swartling, Fredrik, additional

Published
2018
Full Text
View/download PDF

41. MBCL-30. SUBGROUP-DIRECTED CLINICAL AND MOLECULAR STRATIFICATION OF DISEASE RISK IN INFANT MEDULLOBLASTOMA

Author

Hicks, Debbie, primary, Rafiee, Gholamreza, additional, Schwalbe, Edward C, additional, Lindsey, Janet C, additional, Hill, Rebecca M, additional, Smith, Amanda, additional, Crosier, Stephen, additional, Joshi, Abhijit, additional, Robson, Keith, additional, Wharton, Stephen, additional, Jacques, Thomas, additional, Williamson, Daniel, additional, Bailey, Simon, additional, and Clifford, Steven C, additional

Published
2018
Full Text
View/download PDF

43. Development of a targeted sequencing approach to identify prognostic, predictive and diagnostic markers in paediatric solid tumours

Author

Izquierdo, Elisa, primary, Yuan, Lina, additional, George, Sally, additional, Hubank, Michael, additional, Jones, Chris, additional, Proszek, Paula, additional, Shipley, Janet, additional, Gatz, Susanne A., additional, Stinson, Caedyn, additional, Moore, Andrew S., additional, Clifford, Steven C., additional, Hicks, Debbie, additional, Lindsey, Janet C., additional, Hill, Rebecca M., additional, Jacques, Thomas S., additional, Chalker, Jane, additional, Thway, Khin, additional, O’Connor, Simon, additional, Marshall, Lynley, additional, Moreno, Lucas, additional, Pearson, Andrew, additional, Chesler, Louis, additional, Walker, Brian A., additional, and De Castro, David Gonzalez, additional

Published
2017
Full Text
View/download PDF

44. Combined MYC and P53 Defects Emerge at Medulloblastoma Relapse and Define Rapidly Progressive, Therapeutically Targetable Disease

Author

Hill, Rebecca M., Kuijper, Sanne, Lindsey, Janet C., Petrie, Kevin, Schwalbe, Ed C., Barker, Karen, Boult, Jessica K. R., Williamson, Daniel, Ahmad, Zai, Hallsworth, Albert, Ryan, Sarra L., Poon, Evon, Robinson, Simon P., Ruddle, Ruth, Raynaud, Florence I., Howell, Louise, Kwok, Colin, Joshi, Abhijit, Nicholson, Sarah Leigh, Crosier, Stephen, Ellison, David W., Wharton, Stephen B., Robson, Keith, Michalski, Antony, Hargrave, Darren, Jacques, Thomas S., Pizer, Barry, Bailey, Simon, Swartling, Fredrik J., Weiss, William A., Chesler, Louis, Clifford, Steven C., Hill, Rebecca M., Kuijper, Sanne, Lindsey, Janet C., Petrie, Kevin, Schwalbe, Ed C., Barker, Karen, Boult, Jessica K. R., Williamson, Daniel, Ahmad, Zai, Hallsworth, Albert, Ryan, Sarra L., Poon, Evon, Robinson, Simon P., Ruddle, Ruth, Raynaud, Florence I., Howell, Louise, Kwok, Colin, Joshi, Abhijit, Nicholson, Sarah Leigh, Crosier, Stephen, Ellison, David W., Wharton, Stephen B., Robson, Keith, Michalski, Antony, Hargrave, Darren, Jacques, Thomas S., Pizer, Barry, Bailey, Simon, Swartling, Fredrik J., Weiss, William A., Chesler, Louis, and Clifford, Steven C.

Abstract

We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this group died of rapidly progressive disease postrelapse. To study this interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of p53 function in this model produced aggressive tumors that mimicked characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity and genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53-MYC interactions at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically.

Published
2015
Full Text
View/download PDF

45. Combined MYC and P53 Defects Emerge at Medulloblastoma Relapse and Define Rapidly Progressive, Therapeutically Targetable Disease

Author

Hill, Rebecca M., primary, Kuijper, Sanne, additional, Lindsey, Janet C., additional, Petrie, Kevin, additional, Schwalbe, Ed C., additional, Barker, Karen, additional, Boult, Jessica K.R., additional, Williamson, Daniel, additional, Ahmad, Zai, additional, Hallsworth, Albert, additional, Ryan, Sarra L., additional, Poon, Evon, additional, Robinson, Simon P., additional, Ruddle, Ruth, additional, Raynaud, Florence I., additional, Howell, Louise, additional, Kwok, Colin, additional, Joshi, Abhijit, additional, Nicholson, Sarah Leigh, additional, Crosier, Stephen, additional, Ellison, David W., additional, Wharton, Stephen B., additional, Robson, Keith, additional, Michalski, Antony, additional, Hargrave, Darren, additional, Jacques, Thomas S., additional, Pizer, Barry, additional, Bailey, Simon, additional, Swartling, Fredrik J., additional, Weiss, William A., additional, Chesler, Louis, additional, and Clifford, Steven C., additional

Published
2015
Full Text
View/download PDF

46. MYC and TP53 defects interact at medulloblastoma relapse to define rapidly progressive disease and can be targeted therapeutically

Author

Hill, Rebecca M., Kuijper, Sanne, Lindsey, Janet, Schwalbe, Ed C., Barker, Karen, Boult, Jessica, Williamson, Daniel, Ahmad, Zai, Hallsworth, Albert, Ryan, Sarra, Poon, Evon, Robinson, Simon, Ruddle, Ruth, Raynaud, Florence, Howell, Louise, Kwok, Colin, Joshi, Abhijit, Nicholson, Sarah, Crosier, Stephen, Wharton, Stephen, Jacques, Tom, Robson, Keith, Michalski, Antony, Hargrave, Darren, Pizer, Barry, Bailey, Simon, Swartling, Fredrik J., Petrie, Kevin, Weiss, William A., Chesler, Louis, Clifford, Steve, Hill, Rebecca M., Kuijper, Sanne, Lindsey, Janet, Schwalbe, Ed C., Barker, Karen, Boult, Jessica, Williamson, Daniel, Ahmad, Zai, Hallsworth, Albert, Ryan, Sarra, Poon, Evon, Robinson, Simon, Ruddle, Ruth, Raynaud, Florence, Howell, Louise, Kwok, Colin, Joshi, Abhijit, Nicholson, Sarah, Crosier, Stephen, Wharton, Stephen, Jacques, Tom, Robson, Keith, Michalski, Antony, Hargrave, Darren, Pizer, Barry, Bailey, Simon, Swartling, Fredrik J., Petrie, Kevin, Weiss, William A., Chesler, Louis, and Clifford, Steve

Abstract

Abstract nr LB-201

Published
2014
Full Text
View/download PDF

47. Abstract LB-201: MYC and TP53 defects interact at medulloblastoma relapse to define rapidly progressive disease and can be targeted therapeutically

Author

Hill, Rebecca M., primary, Kuijper, Sanne, additional, Lindsey, Janet, additional, Schwalbe, Ed C., additional, Barker, Karen, additional, Boult, Jessica, additional, Williamson, Daniel, additional, Ahmad, Zai, additional, Hallsworth, Albert, additional, Ryan, Sarra, additional, Poon, Evon, additional, Robinson, Simon, additional, Ruddle, Ruth, additional, Raynaud, Florence, additional, Howell, Louise, additional, Kwok, Colin, additional, Joshi, Abhijit, additional, Nicholson, Sarah, additional, Crosier, Stephen, additional, Wharton, Stephen, additional, Jacques, Tom, additional, Robson, Keith, additional, Michalski, Antony, additional, Hargrave, Darren, additional, Pizer, Barry, additional, Bailey, Simon, additional, Swartling, Fredrik J., additional, Petrie, Kevin, additional, Weiss, William A., additional, Chesler, Louis, additional, and Clifford, Steve, additional

Published
2014
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results