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Limitations of current in vitro models for testing the clinical potential of epigenetic inhibitors for treatment of pediatric ependymoma (2018)
Journal Article
Rogers, H. A., Chapman, R., Kings, H., Allard, J., Barron-Hastings, J., Pajtler, K. W., Sill, M., Pfister, S., & Grundy, R. G. (2018). Limitations of current in vitro models for testing the clinical potential of epigenetic inhibitors for treatment of pediatric ependymoma. Oncotarget, 9(92), 36530-36541. https://doi.org/10.18632/oncotarget.26370

Background: Epigenetic modifications have been shown to play an important role in the classification and pathogenesis of the pediatric brain tumor ependymoma, suggesting they are a potential therapeutic target.

Results: Agents targeting epigenetic... Read More about Limitations of current in vitro models for testing the clinical potential of epigenetic inhibitors for treatment of pediatric ependymoma.

Chemical modulation of autophagy as an adjunct to chemotherapy in childhood and adolescent brain tumors (2018)
Journal Article
Servante, J., Estranero, J., Meijer, L., Layfield, R., & Grundy, R. (2018). Chemical modulation of autophagy as an adjunct to chemotherapy in childhood and adolescent brain tumors. Oncotarget, 9(81), 35266-35277. https://doi.org/10.18632/oncotarget.26186

Brain tumors are the leading cause of cancer-related death in children and are the most challenging childhood cancer in relation to diagnosis, treatment, and outcome. One potential novel strategy to improve outcomes in cancer involves the manipulati... Read More about Chemical modulation of autophagy as an adjunct to chemotherapy in childhood and adolescent brain tumors.

Tissue metabolite profiles for the characterisation of paediatric cerebellar tumours (2018)
Journal Article
Bennett, C. D., Kohe, S. E., Gill, S. K., Davies, N. P., Wilson, M., Storer, L. C. D., Ritzmann, T., Paine, S. M. L., Scott, I. S., Nicklaus-Wollenteit, I., Tennant, D. A., Grundy, R. G., & Peet, A. C. (2018). Tissue metabolite profiles for the characterisation of paediatric cerebellar tumours. Scientific Reports, 8, Article 11992. https://doi.org/10.1038/s41598-018-30342-8

Paediatric brain tumors are becoming well characterized due to large genomic and epigenomic studies. Metabolomics is a powerful analytical approach aiding in the characterization of tumors. This study shows that common cerebellar tumors have metaboli... Read More about Tissue metabolite profiles for the characterisation of paediatric cerebellar tumours.

Molecular heterogeneity and CXorf67 alterations in posterior fossa group A (PFA) ependymomas (2018)
Journal Article
Pajtler, K. W., Wen, J., Sill, M., Lin, T., Orisme, W., Tang, B., Hübner, J.-M., Ramaswamy, V., Jia, S., Dalton, J. D., Haupfear, K., Rogers, H. A., Punchihewa, C., Lee, R., Easton, J., Wu, G., Ritzmann, T. A., Chapman, R., Chavez, L., Boop, F. A., …Ellison, D. W. (2018). Molecular heterogeneity and CXorf67 alterations in posterior fossa group A (PFA) ependymomas. Acta Neuropathologica, 136(2), 211-226. https://doi.org/10.1007/s00401-018-1877-0

Of nine ependymoma molecular groups detected by DNA methylation profiling, the posterior fossa type A (PFA) is most prevalent. We used DNA methylation profiling to look for further molecular heterogeneity among 675 PFA ependymomas. Two major subgroup... Read More about Molecular heterogeneity and CXorf67 alterations in posterior fossa group A (PFA) ependymomas.

Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target (2018)
Journal Article
Apps, J. R., Carreno, G., Gonzalez-Meljem, J. M., Haston, S., Guiho, R., Cooper, J. E., Manshaei, S., Jani, N., Holsken, A., Pettorini, B., Beynon, R. J., Simpson, D. M., Fraser, H. C., Hong, Y., Hallang, S., Stone, T. J., Virasami, A., Donson, A. M., Jones, D., Aquilina, K., …Martinez-Barbera, J. P. (2018). Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target. Acta Neuropathologica, 135(5), 757-777. https://doi.org/10.1007/s00401-018-1830-2

Adamantinomatous craniopharyngiomas (ACPs) are clinically challenging tumours, the majority of which have activating mutations in CTNNB1. They are histologically complex, showing cystic and solid components, the latter comprised of different morpholo... Read More about Tumour compartment transcriptomics demonstrates the activation of inflammatory and odontogenic programmes in human adamantinomatous craniopharyngioma and identifies the MAPK/ERK pathway as a novel therapeutic target.

Translating childhood brain tumour research into clinical practice: the experience of molecular classification and diagnostics (2018)
Journal Article
Ritzmann, T. A., & Grundy, R. G. (2018). Translating childhood brain tumour research into clinical practice: the experience of molecular classification and diagnostics. Paediatrics and Child Health, 28(4), https://doi.org/10.1016/j.paed.2018.01.006

Diagnosis and treatment of paediatric brain tumours has shown limited progress over the last half century. However, in the past 10 years the development of molecular techniques for investigating these tumours has expanded exponentially. The use of me... Read More about Translating childhood brain tumour research into clinical practice: the experience of molecular classification and diagnostics.

Transcriptomic analysis in pediatric spinal ependymoma reveals distinct molecular signatures (2017)
Journal Article
Lourdusamy, A., Luo, L. Z., Storer, L. C., Cohen, K. J., Resar, L., & Grundy, R. G. (2017). Transcriptomic analysis in pediatric spinal ependymoma reveals distinct molecular signatures. Oncotarget, 8(70), https://doi.org/10.18632/oncotarget.23311

Pediatric spinal ependymomas (SEPN) are important albeit uncommon malignant central nervous system tumors with limited treatment options. Our current knowledge about the underlying biology of these tumors is limited due to their rarity. To begin to e... Read More about Transcriptomic analysis in pediatric spinal ependymoma reveals distinct molecular signatures.

Evaluation of a novel antibody to define histone 3.3 G34R mutant brain tumours (2017)
Journal Article
Haque, F., Varlet, P., Puntonet, J., Storer, L., Bountali, A., Rahman, R., Grill, J., Carcaboso, A. M., Jones, C., Layfield, R., & Grundy, R. G. (2017). Evaluation of a novel antibody to define histone 3.3 G34R mutant brain tumours. Acta Neuropathologica Communications, 5, 1-9. https://doi.org/10.1186/s40478-017-0449-1

Missense somatic mutations affecting histone H3.1 and H3.3 proteins are now accepted as the hallmark of paediatric diffuse intrinsic pontine gliomas (DIPG), non-brain stem paediatric high grade gliomas (pHGG) as well as a subset of adult glioblastoma... Read More about Evaluation of a novel antibody to define histone 3.3 G34R mutant brain tumours.

Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors (2016)
Journal Article
Torchia, J., Golbourn, B., Feng, S., Ching Ho, K., Sin-Chan, P., Vasiljevic, A., Norman, J. D., Guilhamon, P., Garzia, L., Agamez, N. R., Lu, M., Chan, T. S., Picard, D., de Antonellis, P., Khuong-Quang, D.-A., Planello, A. C., Zeller, C., Barsyte-Lovejoy, D., Lafay-Cousin, L., Letourneau, L., …Huang, A. (2016). Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors. Cancer Cell, 30(6), 891-908. https://doi.org/10.1016/j.ccell.2016.11.003

We recently reported that atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In this study, we anal... Read More about Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors.

Assessing ‘second-look’ tumour resectability in childhood posterior fossa ependymoma—a centralised review panel and staging tool for future studies (2016)
Journal Article
Millward, C. P., Malluci, C., Jaspan, T., Macarthur, D., Heyward, R., Cox, T., Chong, K., & Grundy, R. G. (2016). Assessing ‘second-look’ tumour resectability in childhood posterior fossa ependymoma—a centralised review panel and staging tool for future studies. Child's Nervous System, 32, 2189–2196. https://doi.org/10.1007/s00381-016-3225-9

Molecular subgroups of atypical teratoid rhabdoid tumours in children: an integrated genomic and clinicopathological analysis (2015)
Journal Article
Grundy, R., Torchia, J., Picard, D., Lafay-Cousin, L., Hawkins, C. E., Kim, S.-K., Letourneau, L., Ra, P. Y.-S., Ching Ho, K., Sin Yu Chan, T., Sin-Chan, P., Dunham, C. P., Yip, S., Ng, H.-K., Lu, J.-Q., Albrecht, S., Pimentel, J., Chan, J. A., Somers, G. R., Zielenska, M., … Huang, D. A. (2015). Molecular subgroups of atypical teratoid rhabdoid tumours in children: an integrated genomic and clinicopathological analysis. Lancet Oncology, 16(5), 569-582. https://doi.org/10.1016/S1470-2045%2815%2970114-2

Background
Rhabdoid brain tumours, also called atypical teratoid rhabdoid tumours, are lethal childhood cancers with characteristic genetic alterations of SMARCB1/hSNF5. Lack of biological understanding of the substantial clinical heterogeneity of t... Read More about Molecular subgroups of atypical teratoid rhabdoid tumours in children: an integrated genomic and clinicopathological analysis.

Expression alterations define unique molecular characteristics of spinal ependymomas (2015)
Journal Article
Lourdusamy, A., Rahman, R., & Grundy, R. G. (2015). Expression alterations define unique molecular characteristics of spinal ependymomas. Oncotarget, 6(23), https://doi.org/10.18632/oncotarget.3715

Ependymomas are glial tumors that originate in either intracranial or spinal regions. Although tumors from different regions are histologically similar, they are biologically distinct. We therefore sought to identify molecular characteristics of spin... Read More about Expression alterations define unique molecular characteristics of spinal ependymomas.

Combined hereditary and somatic mutations of replication error repair genes result in rapid onset of ultra-hypermutated cancers (2015)
Journal Article
Grundy, R., Shlien, A., Campbell, B. B., de Borja, R., Alexandrov, L. B., Merico, D., Wedge, D., Van Loo, P., Tarpey, P. S., Coupland, P., Behjati, S., Pollett, A., Lipman, T., Heidari, A., Deshmukh, S., Avitzur, N., Meier, B., Gerstung, M., Hong, Y., Merino, D. M., …Tabori, U. (2015). Combined hereditary and somatic mutations of replication error repair genes result in rapid onset of ultra-hypermutated cancers. Nature Genetics, 47(3), 257-262. https://doi.org/10.1038/ng.3202

DNA replication?associated mutations are repaired by two components: polymerase proofreading and mismatch repair. The mutation consequences of disruption to both repair components in humans are not well studied. We sequenced cancer genomes from child... Read More about Combined hereditary and somatic mutations of replication error repair genes result in rapid onset of ultra-hypermutated cancers.

Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma (2014)
Journal Article
Smith, S. J., Rahman, C. V., Ritchie, A. A., Gould, T. W., Ward, J. H., Shakesheff, K. M., Grundy, R. G., Rahman, R., & Clarke, P. A. (2014). Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma. Annals of The Royal College of Surgeons of England, 96(7), 495-501. https://doi.org/10.1308/003588414X13946184903568

Introduction: The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into th... Read More about Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma.

Germ-line and somatic DICER1 mutations in pineoblastoma (2014)
Journal Article
de Kock, L., Sabbaghian, N., Druker, H., Weber, E., Hamel, N., Miller, S., Choong, C. S., Gottardo, N. G., Kees, U. R., Rednam, S. P., van Hest, L. P., Jongmans, M. C., Jhangiani, S., Lupski, J. R., Zacharin, M., Bouron-Dal Soglio, D., Huang, A., Priest, J. R., Perry, A., Mueller, S., …Foulkes, W. D. (2014). Germ-line and somatic DICER1 mutations in pineoblastoma. Acta Neuropathologica, 128(4), 583–595. https://doi.org/10.1007/s00401-014-1318-7

Germ-line RB-1 mutations predispose to pineoblastoma (PinB), but other predisposing genetic factors are not well established. We recently identified a germ-line DICER1 mutation in a child with a PinB. This was accompanied by loss of heterozygosity (L... Read More about Germ-line and somatic DICER1 mutations in pineoblastoma.

Dissecting DNA repair in adult high grade gliomas for patient stratification in the post-genomic era (2014)
Journal Article
Perry, C., Agarwal, D., Abdel-Fatah, T. M., Lourdusamy, A., Grundy, R., Auer, D. T., Walker, D., Lakhani, R., Scott, I. S., Chan, S., Ball, G., & Madhusudan, S. (2014). Dissecting DNA repair in adult high grade gliomas for patient stratification in the post-genomic era. Oncotarget, 5(14), 5764-5781. https://doi.org/10.18632/oncotarget.2180

Deregulation of multiple DNA repair pathways may contribute to aggressive biology and therapy resistance in gliomas. We evaluated transcript levels of 157 genes involved in DNA repair in an adult glioblastoma Test set (n=191) and validated in ‘The Ca... Read More about Dissecting DNA repair in adult high grade gliomas for patient stratification in the post-genomic era.

Recommendations for assessing cognitive risks in young children treated for ependymoma for clinical and research protocols: evidence from a systematic literature review (2014)
Journal Article
Morrall, M. C., Pitchford, N. J., Waters, E. C., Ablett, K. L., Stocks, H., Walker, D., & Grundy, R. G. (2014). Recommendations for assessing cognitive risks in young children treated for ependymoma for clinical and research protocols: evidence from a systematic literature review. Journal of Pediatric Oncology Nursing, 2(1), https://doi.org/10.14205/2309-3021.2014.02.01.4

Background: Current treatment approaches for pediatric ependymoma differ between North American and European studies. Post-surgical adjuvant irradiation is used in children aged <36 months in North America, whilst European approaches use chemotherapy...

Processed pseudogenes acquired somatically during cancer development (2014)
Journal Article
GRUNDY, R., Provenzano, E., Cooke, S. L., van de Vijver, M., Shlien, A., Richardson, A. L., Marshall, J., Purdie, C., Pipinikas, C. P., Pinder, S., Martincorena, I., Mac Grogan, G., Tubio, J. M., Vincent-Salomon, A., Li, Y., Larsimont, D., Menzies, A., Grabau, D., Mudie, L., Sauer, T., …Hooijer, G. K. (2014). Processed pseudogenes acquired somatically during cancer development. Nature Communications, 5, Article 3644. https://doi.org/10.1038/ncomms4644

Cancer evolves by mutation, with somatic reactivation of retrotransposons being one such mutational process. Germline retrotransposition can cause processed pseudogenes, but whether this occurs somatically has not been evaluated. Here we screen seque... Read More about Processed pseudogenes acquired somatically during cancer development.