Genomic and Functional Approaches to Understanding Cancer Aneuploidy.
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Abstract | Aneuploidy, whole chromosome or chromosome arm imbalance, is a near-universal characteristic of human cancers. In 10,522 cancer genomes from The Cancer Genome Atlas, aneuploidy was correlated with TP53 mutation, somatic mutation rate, and expression of proliferation genes. Aneuploidy was anti-correlated with expression of immune signaling genes, due to decreased leukocyte infiltrates in high-aneuploidy samples. Chromosome arm-level alterations show cancer-specific patterns, including loss of chromosome arm 3p in squamous cancers. We applied genome engineering to delete 3p in lung 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. |
Year of Publication | 2018
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Journal | Cancer Cell
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Volume | 33
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Issue | 4
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Pages | 676-689.e3
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Date Published | 2018 04 09
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ISSN | 1878-3686
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DOI | 10.1016/j.ccell.2018.03.007
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PubMed ID | 29622463
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PubMed Central ID | PMC6028190
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Grant list | R01 CA188228 / CA / NCI NIH HHS / United States
U24 CA210950 / CA / NCI NIH HHS / United States
U24 CA210949 / CA / NCI NIH HHS / United States
R01 CA163722 / CA / NCI NIH HHS / United States
U24 CA210990 / CA / NCI NIH HHS / United States
U24 CA210957 / CA / NCI NIH HHS / United States
R35 CA197568 / CA / NCI NIH HHS / United States
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