The integrated genomic and epigenomic landscape of brainstem glioma

Lee H. Chen, Changcun Pan, Bill H. Diplas, Cheng Xu, Landon J. Hansen, Yuliang Wu, Xin Chen, Yibo Geng, Tao Sun, Yu Sun, Peng Zhang, Zhen Wu, Junting Zhang, Deling Li, Yang Zhang, Wenhao Wu, Yu Wang, Guangyu Li, Jie Yang, Xiaoyue Wang, Ce Xu, Sizhen Wang, Matthew S. Waitkus, Yiping He, Roger E. McLendon, David M. Ashley, Hai Yan () and Liwei Zhang ()
Additional contact information
Lee H. Chen: Duke University Medical Center
Changcun Pan: Capital Medical University
Bill H. Diplas: Duke University Medical Center
Cheng Xu: Duke University Medical Center
Landon J. Hansen: Duke University Medical Center
Yuliang Wu: Capital Medical University
Xin Chen: Capital Medical University
Yibo Geng: Capital Medical University
Tao Sun: Capital Medical University
Yu Sun: Capital Medical University
Peng Zhang: Capital Medical University
Zhen Wu: Capital Medical University
Junting Zhang: Capital Medical University
Deling Li: Capital Medical University
Yang Zhang: Capital Medical University
Wenhao Wu: Capital Medical University
Yu Wang: Capital Medical University
Guangyu Li: Genetron Health (Beijing) Co. Ltd
Jie Yang: Genetron Health (Beijing) Co. Ltd
Xiaoyue Wang: Peking Union Medical College
Ce Xu: Genetron Health (Beijing) Co. Ltd
Sizhen Wang: Genetron Health (Beijing) Co. Ltd
Matthew S. Waitkus: Duke University Medical Center
Yiping He: Duke University Medical Center
Roger E. McLendon: Duke University Medical Center
David M. Ashley: Duke University Medical Center
Hai Yan: Duke University Medical Center
Liwei Zhang: Capital Medical University

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract Brainstem gliomas are a heterogeneous group of tumors that encompass both benign tumors cured with surgical resection and highly lethal cancers with no efficacious therapies. We perform a comprehensive study incorporating epigenetic and genomic analyses on a large cohort of brainstem gliomas, including Diffuse Intrinsic Pontine Gliomas. Here we report, from DNA methylation data, distinct clusters termed H3-Pons, H3-Medulla, IDH, and PA-like, each associated with unique genomic and clinical profiles. The majority of tumors within H3-Pons and-H3-Medulla harbors H3F3A mutations but shows distinct methylation patterns that correlate with anatomical localization within the pons or medulla, respectively. Clinical data show significantly different overall survival between these clusters, and pathway analysis demonstrates different oncogenic mechanisms in these samples. Our findings indicate that the integration of genetic and epigenetic data can facilitate better understanding of brainstem gliomagenesis and classification, and guide future studies for the development of novel treatments for this disease.

Date: 2020
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DOI: 10.1038/s41467-020-16682-y

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