Pediatric high-grade glioma: biologically and clinically in need of new thinking

Chris Jones¹, Matthias A Karajannis², David T W Jones³, Mark W Kieran⁴, Michelle Monje⁵, Suzanne J Baker⁶, Oren J Becher⁷, Yoon-Jae Cho⁵, Nalin Gupta⁸, Cynthia Hawkins⁹, Darren Hargrave¹⁰, Daphne A Haas-Kogan¹¹, Nada Jabado¹², Xiao-Nan Li¹³, Sabine Mueller⁸, Theo Nicolaides⁸, Roger J Packer¹⁴, Anders I Persson⁸, Joanna J Phillips⁸, Erin F Simonds⁸, James M Stafford¹⁵, Yujie Tang¹⁶, Stefan M Pfister^{3

17}, William A Weiss⁸

Affiliations

¹ Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, London, UK.
² Division of Pediatric Hematology/Oncology, NYU Langone Medical Center, New York, NY, USA.
³ Division of Pediatric Neurooncology, German Cancer Research Centre, Heidelberg, Germany.
⁴ Pediatric Medical Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
⁵ Department of Neurology & Neurological Sciences, Stanford University, Stanford, California, USA.
⁶ Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
⁷ Departments of Pediatrics and Pathology, Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina, USA.
⁸ Departments of Pediatrics, Neurology, and Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
⁹ The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Canada.
¹⁰ Neuro-oncology and Experimental Therapeutics, Great Ormond Street Hospital for Children, London, UK.
¹¹ Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
¹² Department of Pediatrics, McGill University, Montreal, Canada.
¹³ Brain Tumor Program, Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
¹⁴ Center for Neuroscience and Behavioral Medicine, Children's National Health System, Washington, District of Columbia, USA.
¹⁵ Department of Biochemistry, NYU Langone Medical Center, New York, New York, USA.
¹⁶ Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
¹⁷ Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany.

PMID: 27282398
PMCID: PMC5464243
DOI: 10.1093/neuonc/now101

Review

Pediatric high-grade glioma: biologically and clinically in need of new thinking

Chris Jones et al. Neuro Oncol. 2017.

. 2017 Feb 1;19(2):153-161.

doi: 10.1093/neuonc/now101.

Authors

Affiliations

¹ Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, London, UK.
² Division of Pediatric Hematology/Oncology, NYU Langone Medical Center, New York, NY, USA.
³ Division of Pediatric Neurooncology, German Cancer Research Centre, Heidelberg, Germany.
⁴ Pediatric Medical Neuro-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
⁵ Department of Neurology & Neurological Sciences, Stanford University, Stanford, California, USA.
⁶ Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
⁷ Departments of Pediatrics and Pathology, Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina, USA.
⁸ Departments of Pediatrics, Neurology, and Neurological Surgery, University of California San Francisco, San Francisco, California, USA.
⁹ The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Canada.
¹⁰ Neuro-oncology and Experimental Therapeutics, Great Ormond Street Hospital for Children, London, UK.
¹¹ Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
¹² Department of Pediatrics, McGill University, Montreal, Canada.
¹³ Brain Tumor Program, Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
¹⁴ Center for Neuroscience and Behavioral Medicine, Children's National Health System, Washington, District of Columbia, USA.
¹⁵ Department of Biochemistry, NYU Langone Medical Center, New York, New York, USA.
¹⁶ Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
¹⁷ Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany.

PMID: 27282398
PMCID: PMC5464243
DOI: 10.1093/neuonc/now101 (V体育安卓版)

VSports app下载 - Abstract

High-grade gliomas in children are different from those that arise in adults. Recent collaborative molecular analyses of these rare cancers have revealed previously unappreciated connections among chromatin regulation, developmental signaling, and tumorigenesis VSports手机版. As we begin to unravel the unique developmental origins and distinct biological drivers of this heterogeneous group of tumors, clinical trials need to keep pace. It is important to avoid therapeutic strategies developed purely using data obtained from studies on adult glioblastoma. This approach has resulted in repetitive trials and ineffective treatments being applied to these children, with limited improvement in clinical outcome. The authors of this perspective, comprising biology and clinical expertise in the disease, recently convened to discuss the most effective ways to translate the emerging molecular insights into patient benefit. This article reviews our current understanding of pediatric high-grade glioma and suggests approaches for innovative clinical management. .

Keywords: DIPG; clinical trials; genomics; glioma; pediatric. V体育安卓版.

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**Fig. 1.**
*Biologically and clinically defined subgroups of pediatric infiltrating glioma*. Specific, selective, recurrent, and mutually exclusive mutations in the genes encoding the histone H3.3 (*H3F3A*) and H3.1 (*HIST1H3B*, *HIST1H3C*) variants, along with *BRAF* V600E, mark distinct subgroups of disease in children and young adults. There are clear differences in location, age at presentation, clinical outcome, gender distribution, predominant histology and concurrent epigenetic and genetic alterations. The remaining half of tumors comprising these diseases harbor numerous, partially overlapping putative drivers or other (epi)genomic characteristics, but as yet do not form well-validated biological and clinical subgroups. The small proportion of children (mostly adolescents) with *IDH1* mutations represent the lower tail of age distribution of an otherwise adult subgroup, and are excluded here.

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"VSports最新版本" References

1. Northcott PA, Pfister SM, Jones DT. Next-generation (epi)genetic drivers of childhood brain tumours and the outlook for targeted therapies. Lancet Oncol. 2015;16(6):e293–e302. - PubMed
1. Jones C, Baker SJ. Unique genetic and epigenetic mechanisms driving paediatric diffuse high-grade glioma. Nat Rev Cancer. 2014;14(10):651–661. - PMC (V体育平台登录) - PubMed
1. Northcott PA, Jones DT, Kool M et al. . Medulloblastomics: the end of the beginning. Nat Rev Cancer. 2012;12(12):818–834. - PMC - PubMed
1. Pajtler KW, Witt H, Sill M et al. . Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups. Cancer Cell. 2015;27(5):728–743. - PMC - PubMed
1. Sturm D, Bender S, Jones DT et al. . Paediatric and adult glioblastoma: multiform (epi)genomic culprits emerge. Nat Rev Cancer. 2014;14(2):92–107. - PMC - PubMed

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Pediatric high-grade glioma: biologically and clinically in need of new thinking

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Pediatric high-grade glioma: biologically and clinically in need of new thinking

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