Dataset Information

The integrated genomic and epigenomic landscape of brainstem glioma.

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.

SUBMITTER: Chen LH

PROVIDER: S-EPMC7299931 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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The integrated genomic and epigenomic landscape of brainstem glioma.

Chen Lee H LH Pan Changcun C Diplas Bill H BH Xu Cheng C Hansen Landon J LJ Wu Yuliang Y Chen Xin X Geng Yibo Y Sun Tao T Sun Yu Y Zhang Peng P Wu Zhen Z Zhang Junting J Li Deling D Zhang Yang Y Wu Wenhao W Wang Yu Y Li Guangyu G Yang Jie J Wang Xiaoyue X Xu Ce C Wang Sizhen S Waitkus Matthew S MS He Yiping Y McLendon Roger E RE Ashley David M DM Yan Hai H Zhang Liwei L

Nature communications 20200617 1

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 profi ...[more]

PMID: 32555164

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Project description:BackgroundMajority of prostate cancer (PCa) deaths are attributed to localized high-grade aggressive tumours which progress rapidly to metastatic disease. A critical unmet need in clinical management of PCa is discovery and characterization of the molecular drivers of aggressive tumours. The development and progression of aggressive PCa involve genetic and epigenetic alterations occurring in the germline, somatic (tumour), and epigenomes. To date, interactions between genes containing germline, somatic, and epigenetic mutations in aggressive PCa have not been characterized. The objective of this investigation was to elucidate the genomic-epigenomic interaction landscape in aggressive PCa to identify potential drivers aggressive PCa and the pathways they control. We hypothesized that aggressive PCa originates from a complex interplay between genomic (both germline and somatic mutations) and epigenomic alterations. We further hypothesized that these complex arrays of interacting genomic and epigenomic factors affect gene expression, molecular networks, and signaling pathways which in turn drive aggressive PCa.MethodsWe addressed these hypotheses by performing integrative data analysis combining information on germline mutations from genome-wide association studies with somatic and epigenetic mutations from The Cancer Genome Atlas using gene expression as the intermediate phenotype.ResultsThe investigation revealed signatures of genes containing germline, somatic, and epigenetic mutations associated with aggressive PCa. Aberrant DNA methylation had effect on gene expression. In addition, the investigation revealed molecular networks and signalling pathways enriched for germline, somatic, and epigenetic mutations including the STAT3, PTEN, PCa, ATM, AR, and P53 signalling pathways implicated in aggressive PCa.ConclusionsThe study demonstrated that integrative analysis combining diverse omics data is a powerful approach for the discovery of potential clinically actionable biomarkers, therapeutic targets, and elucidation of oncogenic interactions between genomic and epigenomic alterations in aggressive PCa.

Dataset Information

The integrated genomic and epigenomic landscape of brainstem glioma.

Publications

The integrated genomic and epigenomic landscape of brainstem glioma.

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