Three-dimensional genome landscape of primary human cancers

Citation TBD.

Genome conformation underlies transcriptional regulation by distal enhancers, and genomic rearrangements in cancer can alter critical regulatory interactions. Here we profiled the 3D genome architecture and enhancer connectome of 69 tumor samples spanning 15 primary human cancer types from The Cancer Genome Atlas (TCGA). We discovered three archetypes of enhancer usage for over one hundred oncogenes across human cancers: static, selective gain, or dynamic rewiring. Integrative analyses revealed the enhancer landscape of non-cancer cells in the tumor microenvironment at genes related to immune escape. Deep whole genome sequencing and enhancer connectome mapping provided accurate detection and validation of diverse structural variants across cancer genomes, and revealed distinct enhancer rewiring consequences from noncoding point mutations, genomic inversions, translocations, and focal amplifications. Extrachromosomal DNA promoted more extensive enhancer rewiring of oncogenes among several types of focal amplification mechanisms. These results suggest a systematic approach to understand genome topology in cancer etiology and therapy.

Data in the GDC

• GDC Supplemental Manifests
  
  • Open-Access Data - Download Manifest (15 Files)
  • Controlled-Access Data - Download Manifest (6 Files)

Supplemental Data

• WGS_metadata.txt - WGS file metadata
• WGS_ASCAT_CNV_calls.tar.gz - WGS CNV calls (ASCAT)
• ASCAT_ploidy_normalized.txt - WGS ploidy normalized CNV calls (ASCAT)
• WGS_BRASS_SV_calls.tar.gz - WGS SV calls (BRASS)
• WGS_CaVEMan_SNV_calls.tar.gz - WGS SNV calls (CaVEMan)
• WGS_pindel_indel_calls.tar.gz - WGS indel calls (pindel)
• AA_output_insert_sdevs_9.tar.gz - AmpliconArchitect focal amplication output files
• AC_output_insert_sdevs_9.tar.gz - AmpliconClassifier focal amplication output files
• TCGA_HiChIP_metadata.txt - HiChIP file metadata
• TCGA_HiChIP_allValidPairs.tar.gz - HiChIP allValidPairs files (HiC-Pro)
• TCGA_HiChIP_hic.tar.gz - HiChIP .hic files (Juicer)
• TCGA_HiChIP_FitHiChIP_loop_calls.tar.gz - HiChIP per sample loop calls (FitHiChIP)
• TCGA_HiChIP_1Dsignal_bw.tar.gz - HiChIP 1D H3K27ac signal bigwig files
• TCGA_HiChIP_1Dsignal_peaks.tar.gz - HiChIP 1D H3K27ac signal narrowPeak calls (MACS2)
• TCGA_HiChIP_1D_signal_raw_counts.txt.gz - HiChIP 1D H3K27ac signal raw counts (union peak set)
• TCGA_HiChIP_1D_signal_norm_counts.txt.gz - HiChIP 1D H3K27ac signal normalized counts (union peak set)
• TCGA_HiChIP_1D_signal_CNV_corrected_norm_counts.txt.gz - HiChIP 1D H3K27ac signal CNV corrected normalized counts (union peak set)
• TCGA_HiChIP_FitHiChIP_interactions_raw_counts.txt.gz - HiChIP FitHiChIP interactions raw counts (union loop set)
• TCGA_HiChIP_FitHiChIP_interactions_norm_counts.txt.gz  - HiChIP FitHiChIP interactions normalized counts (union loop set)
• TCGA_HiChIP_FitHiChIP_interactions_CNV_corrected_norm_counts.txt.gz - HiChIP FitHiChIP interactions CNV corrected normalized counts (union loop set)
• HiChIP_SNV_POS.xlsx - Matched mutation position and allele frequency in HiChIP