A pediatric brain tumor atlas of genes deregulated by somatic genomic rearrangement.
Yiqun ZhangFengju ChenLawrence A DonehowerMichael E ScheurerChad J CreightonPublished in: Nature communications (2021)
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.
Keyphrases
- genome wide
- copy number
- genome wide identification
- dna methylation
- transcription factor
- gene expression
- single cell
- dna damage response
- genome wide analysis
- poor prognosis
- signaling pathway
- young adults
- small cell lung cancer
- oxidative stress
- childhood cancer
- tyrosine kinase
- rna seq
- multiple sclerosis
- binding protein
- pi k akt
- long non coding rna
- epidermal growth factor receptor
- dna repair
- nuclear factor
- inflammatory response
- bioinformatics analysis