A pediatric brain tumor atlas of genes deregulated by somatic genomic rearrangement.

TitleA pediatric brain tumor atlas of genes deregulated by somatic genomic rearrangement.
Publication TypeJournal Article
Year of Publication2021
AuthorsZhang, Y, Chen, F, Donehower, LA, Scheurer, ME, Creighton, CJ
JournalNat Commun
Date Published2021 Feb 10
KeywordsBrain Neoplasms, Cohort Studies, Exome Sequencing, Gene Expression Regulation, Neoplastic, Gene Rearrangement, Genomics, Humans, Mutation, Pediatrics, Sequence Analysis, RNA

The global impact of somatic structural variants (SSVs) on gene expression in pediatric brain tumors has not been thoroughly characterised. Here, using whole-genome and RNA sequencing from 854 tumors of more than 30 different types from the Children's Brain Tumor Tissue Consortium, we report the altered expression of hundreds of genes in association with the presence of nearby SSV breakpoints. SSV-mediated expression changes involve gene fusions, altered cis-regulation, or gene disruption. SSVs considerably extend the numbers of patients with tumors somatically altered for critical pathways, including receptor tyrosine kinases (KRAS, MET, EGFR, NF1), Rb pathway (CDK4), TERT, MYC family (MYC, MYCN, MYB), and HIPPO (NF2). Compared to initial tumors, progressive or recurrent tumors involve a distinct set of SSV-gene associations. High overall SSV burden associates with TP53 mutations, histone H3.3 gene H3F3C mutations, and the transcription of DNA damage response genes. Compared to adult cancers, pediatric brain tumors would involve a different set of genes with SSV-altered cis-regulation. Our comprehensive and pan-histology genomic analyses reveal SSVs to play a major role in shaping the transcriptome of pediatric brain tumors.

Alternate JournalNat Commun
PubMed ID33568653
PubMed Central IDPMC7876141
Grant ListP30 CA125123 / CA / NCI NIH HHS / United States

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