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Genomic and Functional Approaches to Understanding Cancer Aneuploidy.

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.

SUBMITTER: Taylor AM

PROVIDER: S-EPMC6028190 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Genomic and Functional Approaches to Understanding Cancer Aneuploidy.

Taylor Alison M AM Shih Juliann J Ha Gavin G Gao Galen F GF Zhang Xiaoyang X Berger Ashton C AC Schumacher Steven E SE Wang Chen C Hu Hai H Liu Jianfang J Lazar Alexander J AJ Cherniack Andrew D AD Beroukhim Rameen R Meyerson Matthew M

Cancer cell 20180402 4

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 chr ...[more]

PMID: 29622463

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