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Genomic and functional approaches to understanding cancer aneuploidy

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Title: Genomic and functional approaches to understanding cancer aneuploidy
Authors: 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
Item Type: Journal Article
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.
Issue Date: 9-Apr-2018
Date of Acceptance: 6-Mar-2018
URI: http://hdl.handle.net/10044/1/71214
DOI: https://doi.org/10.1016/j.ccell.2018.03.007
ISSN: 1535-6108
Publisher: Elsevier
Start Page: 676
End Page: 689.e3
Journal / Book Title: Cancer Cell
Volume: 33
Issue: 4
Copyright Statement: © 2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Sponsor/Funder: SAIC-F-Frederick, Inc
Leidos Biomedical Research, Inc.
Funder's Grant Number: TCGA Pilot Program
15Y011ST
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
Cell Biology
SQUAMOUS-CELL CARCINOMAS
COPY-NUMBER ALTERATION
CHROMOSOMAL INSTABILITY
EXPRESSION PROFILES
LUNG-CANCER
LANDSCAPE
REVEALS
PROLIFERATION
DELETIONS
MULTIPLE
aneuploidy
cancer genomics
genome engineering
lung squamous cell carcinoma
Aneuploidy
Carcinoma, Squamous Cell
Cell Cycle
Cell Proliferation
Chromosome Aberrations
Chromosome Deletion
Chromosomes, Human, Pair 3
Databases, Genetic
Genomics
Humans
Mutation Rate
Tumor Suppressor Protein p53
Cancer Genome Atlas Research Network
Chromosomes, Human, Pair 3
Humans
Carcinoma, Squamous Cell
Chromosome Aberrations
Aneuploidy
Chromosome Deletion
Genomics
Cell Cycle
Cell Proliferation
Databases, Genetic
Tumor Suppressor Protein p53
Mutation Rate
Science & Technology
Life Sciences & Biomedicine
Oncology
Cell Biology
SQUAMOUS-CELL CARCINOMAS
COPY-NUMBER ALTERATION
CHROMOSOMAL INSTABILITY
EXPRESSION PROFILES
LUNG-CANCER
LANDSCAPE
REVEALS
PROLIFERATION
DELETIONS
MULTIPLE
Oncology & Carcinogenesis
1112 Oncology and Carcinogenesis
1109 Neurosciences
Publication Status: Published
Open Access location: https://www.cancercell.org/retrieve/pii/S1535610818301119
Online Publication Date: 2018-04-02
Appears in Collections:Department of Surgery and Cancer