基因组和功能方法研究癌症非整倍性。
Genomic and Functional Approaches to Understanding Cancer Aneuploidy.
机构信息
Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Cancer Program, Broad Institute, 415 Main Street, Cambridge, MA 02142, USA; Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
Cancer Program, Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
出版信息
Cancer Cell. 2018 Apr 9;33(4):676-689.e3. doi: 10.1016/j.ccell.2018.03.007. Epub 2018 Apr 2.
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.
非整倍体，即整条染色体或染色体臂的不平衡，是人类癌症的一个普遍特征。在癌症基因组图谱（The Cancer Genome Atlas）的 10522 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的表达相关。由于高非整倍体样本中白细胞浸润减少，非整倍体与免疫信号基因的表达呈负相关。染色体臂水平的改变表现出癌症特异性模式，包括鳞状癌中染色体 3p 臂的缺失。我们应用基因组工程技术在肺细胞中删除 3p，导致增殖减少，部分通过 3 号染色体的重复得到挽救。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。
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