Epigenomic landscape and 3D genome structure in pediatric high-grade glioma

Juan Wang, Tina Yi Ting Huang, Ye Hou, Elizabeth Bartom, Xinyan Lu, Ali Shilatifard, Feng Yue*, Amanda Saratsis

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Pediatric high-grade gliomas (pHGGs), including glioblastoma multiforme (GBM) and diffuse intrinsic pontine glioma (DIPG), are morbid brain tumors. Even with treatment survival is poor, making pHGG the number one cause of cancer death in children. Up to 80% of DIPGs harbor a somatic missense mutation in genes encoding histone H3. To investigate whether H3K27M is associated with distinct chromatin structure that alters transcription regulation, we generated the first high-resolution Hi-C maps of pHGG cell lines and tumor tissue. By integrating transcriptome (RNA-seq), enhancer landscape (ChIP-seq), genome structure (Hi-C), and chromatin accessibility (ATAC-seq) datasets from H3K27M and wild-type specimens, we identified tumor-specific enhancers and regulatory networks for known oncogenes. We identified genomic structural variations that lead to potential enhancer hijacking and gene coamplification, including A2M, JAG2, and FLRT1. Together, our results imply three-dimensional genome alterations may play a critical role in the pHGG epigenetic landscape and contribute to tumorigenesis.

Original languageEnglish (US)
Article numbereabg4126
JournalScience Advances
Volume7
Issue number23
DOIs
StatePublished - Jun 2021

ASJC Scopus subject areas

  • General

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