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Genomic and Functional Approaches to Understanding Cancer Aneuploidy.

Genomic and Functional Approaches to Understanding Cancer Aneuploidy.
Author Information (click to view)

Taylor AM, Shih J, Ha G, Gao GF, Zhang X, Berger AC, Schumacher SE, Wang C, Hu H, Liu J, Lazar AJ, , Cherniack AD, Beroukhim R, Meyerson M,


Taylor AM, Shih J, Ha G, Gao GF, Zhang X, Berger AC, Schumacher SE, Wang C, Hu H, Liu J, Lazar AJ, , Cherniack AD, Beroukhim R, Meyerson M, (click to view)

Taylor AM, Shih J, Ha G, Gao GF, Zhang X, Berger AC, Schumacher SE, Wang C, Hu H, Liu J, Lazar AJ, , Cherniack AD, Beroukhim R, Meyerson M,

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Cancer cell 2018 04 0233(4) 676-689.e3 pii 10.1016/j.ccell.2018.03.007

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.

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