TY - JOUR
T1 - Genomic and Functional Approaches to Understanding Cancer Aneuploidy
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 - Hu, Hai
AU - Liu, Jianfang
AU - Lazar, Alexander J.
AU - Caesar-Johnson, Samantha J.
AU - Demchok, John A.
AU - Felau, Ina
AU - Kasapi, Melpomeni
AU - Ferguson, Martin L.
AU - Hutter, Carolyn M.
AU - Sofia, Heidi J.
AU - Tarnuzzer, Roy
AU - Wang, Zhining
AU - Yang, Liming
AU - Zenklusen, Jean C.
AU - Zhang, Jiashan (Julia)
AU - Chudamani, Sudha
AU - Liu, Jia
AU - Lolla, Laxmi
AU - Naresh, Rashi
AU - Pihl, Todd
AU - Sun, Qiang
AU - Wan, Yunhu
AU - Wu, Ye
AU - Cho, Juok
AU - DeFreitas, Timothy
AU - Frazer, Scott
AU - Gehlenborg, Nils
AU - Getz, Gad
AU - Heiman, David I.
AU - Kim, Jaegil
AU - Lawrence, Michael S.
AU - Lin, Pei
AU - Meier, Sam
AU - Noble, Michael S.
AU - Saksena, Gordon
AU - Voet, Doug
AU - Zhang, Hailei
AU - Bernard, Brady
AU - Chambwe, Nyasha
AU - Dhankani, Varsha
AU - Knijnenburg, Theo
AU - Mann, Graham
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
UR - http://www.scopus.com/inward/record.url?scp=85044906084&partnerID=8YFLogxK
U2 - 10.1016/j.ccell.2018.03.007
DO - 10.1016/j.ccell.2018.03.007
M3 - Article
SN - 1535-6108
VL - 33
SP - 676-689.e3
JO - Cancer Cell
JF - Cancer Cell
IS - 4
ER -