Genomic and Functional Approaches to Understanding Cancer Aneuploidy.

Genomic and Functional Approaches to Understanding Cancer Aneuploidy.
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DOI:
10.1016/j.ccell.2018.03.007
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发表时间:
2018-04-09
期刊:
影响因子:
50.3
通讯作者:
Meyerson M
Meyerson M
中科院分区:
医学1区
文献类型:
--
作者:
Taylor AM;Shih J;Ha G;Gao GF;Zhang X;Berger AC;Schumacher SE;Wang C;Hu H;Liu J;Lazar AJ;Cancer Genome Atlas Research Network;Cherniack AD;Beroukhim R;Meyerson M

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非整倍性,即整个染色体或染色体臂不平衡,是人类癌症的一个几乎普遍的特征。在来自癌症基因组图谱(TCGA)的10,522个癌症基因组中,非整倍体与TP53突变,体细胞突变率和增殖基因表达相关。非整倍体与免疫信号基因的表达呈反相关,这是由于在高非整倍体样本中白细胞浸润减少。染色体臂水平的改变显示癌症特异性模式,包括鳞状细胞癌中染色体臂3p的丢失。我们应用基因组工程删除肺细胞中的3p,导致部分由3号染色体复制拯救的增殖减少。本研究定义了癌症非整倍体的基因组和表型相关性,并提供了一种研究染色体臂非整倍体的实验方法。
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 (TCGA), 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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