Cancer Cell. 33 p1-14, 2 April 2018 10.1016/j.ccell.2018.03.007
Aneuploidy, whole chromosome or chromosome arm copy number imbalance, is a near-universal characteristic of human cancers. Here, we apply new genomic and experimental methods to study this little-understood phenomenon. In 10,522 cancer genomes from The Cancer Genome Atlas (TCGA), we found aneuploidy to be positively correlated with TP53 mutation, overall somatic mutation rate, and the expression of genes in proliferation-related pathways. Aneuploidy was anti-correlated with the expression of immune signaling genes, due to decreased leukocyte infiltrates in high-aneuploidy samples. Chromosome arm-level alterations occur in 78% of the TCGA cancers and show cancer-specific patterns; for example, loss of chromosome arm 3p is common in squamous cancers. We applied genome engineering to delete chromosome arm 3p in lung epithelial cells, causing decreased proliferation rescued in part by chromosome 3 duplication. This study defines genomic and phenotypic correlates of cancer aneuploidy and provides an experimental approach to study chromosome arm aneuploidy.
Data in the GDC
- GDC Manifests
- Open-Access Data - Download Manifest (9 Files)
- Controlled-Access Data - Download Manifest (1 File)
Supplemental Data
- MAF Files
- ABSOLUTE-annotated MAF file - TCGA_consolidated.abs_mafs_truncated.fixed.txt.gz
- Miscellaneous Files
- SNP6 whitelisted copy number segments file - broad.mit.edu_PANCAN_Genome_Wide_SNP_6_whitelisted.seg
- GISTIC2.0 all_thresholded.by_genes file - all_thresholded.by_genes_whitelisted.tsv
- GISTIC2.0 all_data_by_genes file - all_data_by_genes_whitelisted.tsv
- ISAR-corrected SNP6 whitelisted copy number segments file - ISAR_corrected.PANCAN_Genome_Wide_SNP_6_whitelisted.seg
- ISAR-corrected GISTIC2.0 all_thresholded.by_genes file - ISAR_GISTIC.all_thresholded.by_genes.txt
- gzipped ISAR-corrected GISTIC2.0 all_data_by_genes file - ISAR_GISTIC.all_data_by_genes.txt.gz
- ABSOLUTE-annotated seg file - TCGA_mastercalls.abs_segtabs.fixed.txt
- ABSOLUTE purity/ploidy file - TCGA_mastercalls.abs_tables_JSedit.fixed.txt
- Aneuploidy scores and arm calls file - PANCAN_ArmCallsAndAneuploidyScore_092817.txt
Additional Resources
- cBioPortal for Cancer Genomics (link is external) Memorial Sloan-Kettering Cancer Center
- PanCanAtlas Additional Files
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Open Access Data
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Controlled Access Data
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