Integrative eQTL-based analyses reveal the biology of breast cancer risk loci.
Integrative eQTL-based analyses reveal the biology of breast cancer risk loci.
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DOI：
10.1016/j.cell.2012.12.034
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发表时间：
2013-01-31
期刊：
影响因子：
64.5
通讯作者：
Freedman ML
中科院分区：
文献类型：
--
作者：
Li Q;Seo JH;Stranger B;McKenna A;Pe'er I;Laframboise T;Brown M;Tyekucheva S;Freedman ML
由于体细胞获得性改变引起的转录调控的复杂性，对肿瘤中基因表达的生殖系决定因素的研究较少。我们使用癌症基因组图谱（TCGA）中提供的多水平信息进行了基于表达数量性状基因座（eQTL）的分析。在我们测量的因素中，顺式作用eQTL占肿瘤基因表达总变异的1.2%，而体细胞拷贝数改变和CpG甲基化分别占7.3%和3.3%。对15个先前报道的乳腺癌风险基因座的eQTL分析导致发现了与转录水平显著相关的三个变体（FDR<0.1）。在一项新的基于反式的分析中，确定了另外三个风险基因座通过ESR1、MYC和KLF4起作用。这些发现提供了乳腺癌中基因表达决定因素的更全面的图片，以及对乳腺癌风险位点的潜在生物学的见解。
Germline determinants of gene expression in tumors are less studied due to the complexity of transcript regulation caused by somatically acquired alterations. We performed expression quantitative trait locus (eQTL) based analyses using the multi-level information provided in The Cancer Genome Atlas (TCGA). Of the factors we measured, cis-acting eQTL saccounted for 1.2% of the total variation of tumor gene expression, while somatic copy number alteration and CpG methylation accounted for 7.3% and 3.3%, respectively. eQTL analyses of 15 previously reported breast cancer risk loci resulted in discovery of three variants that are significantly associated with transcript levels (FDR<0.1). In a novel trans- based analysis, an additional three risk loci were identified to act through ESR1, MYC, and KLF4. These findings provide a more comprehensive picture of gene expression determinants in breast cancer as well as insights into the underlying biology of breast cancer risk loci.
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影响因子：
64.8
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DOI：
10.1073/pnas.1200853109
发表时间：
2012-07-10
影响因子：
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