TY - JOUR
T1 - Genomic and Functional Approaches to Understanding Cancer Aneuploidy
AU - The Cancer Genome Atlas Research Network
AU - Taylor, Alison M.
AU - Shih, Juliann
AU - Ha, Gavin
AU - Gao, Galen F.
AU - Zhang, Xiaoyang
AU - Berger, Ashton C.
AU - Schumacher, Steven E.
AU - Wang, Chen
AU - Lazar, Alexander J.
AU - Liu, Yuexin
AU - Zhang, Wei
AU - Akbani, Rehan
AU - Broom, Bradley M.
AU - Ju, Zhenlin
AU - Kanchi, Rupa Sridevi
AU - Korkut, Anil
AU - Li, Jun
AU - Liang, Han
AU - Ling, Shiyun
AU - Liu, Wenbin
AU - Lu, Yiling
AU - Mills, Gordon B
AU - Uppore Kukkillaya, Arvind Rao
AU - Weinstein, John N.
AU - Zhang, Jiexin
AU - Liu, Xiuping
AU - Wang, Linghua
AU - Fregnani, José Humberto T. G.
AU - Reis, Rui M. V.
AU - Ajani, Jaffer A.
AU - Behrens, Carmen
AU - Bondaruk, Jolanta
AU - Broaddus, Russell
AU - Czerniak, Bogdan
AU - Esmaeli, Bita
AU - Fujimoto, Junya
AU - Gershenwald, Jeffrey
AU - Guo, Charles
AU - Logothetis, Christopher
AU - Meric-Bernstam, Funda
AU - Moran, Cesar
AU - Ramondetta, Lois
AU - Rice, David
AU - Sood, Anil
AU - Tamboli, Pheroze
AU - Thompson, Timothy
AU - Troncoso, Patricia
AU - Tsao, Anne
AU - Wistuba, Ignacio
AU - von Deimling, Andreas
N1 - Publisher Copyright:
© 2018 The Authors
PY - 2018/4/9
Y1 - 2018/4/9
N2 - 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. Analyzing >10,000 human cancers, Taylor et al. show that aneuploidy is correlated with somatic mutation rate, expression of proliferation genes, and decreased leukocyte infiltration. Loss of chromosome arm 3p is common in squamous cancers, but deletion of chromosome 3p reduces cell proliferation in vitro.
AB - 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. Analyzing >10,000 human cancers, Taylor et al. show that aneuploidy is correlated with somatic mutation rate, expression of proliferation genes, and decreased leukocyte infiltration. Loss of chromosome arm 3p is common in squamous cancers, but deletion of chromosome 3p reduces cell proliferation in vitro.
KW - aneuploidy
KW - cancer genomics
KW - genome engineering
KW - lung squamous cell carcinoma
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U2 - 10.1016/j.ccell.2018.03.007
DO - 10.1016/j.ccell.2018.03.007
M3 - Article
C2 - 29622463
AN - SCOPUS:85044906084
SN - 1535-6108
VL - 33
SP - 676-689.e3
JO - Cancer cell
JF - Cancer cell
IS - 4
ER -