在结直肠癌中,假定的cis-regulatory驱动因素
Halit Ongen1, Claus L Andersen2, Jesper B Bramsen2
11] Department of Genetic Medicine and Development, University of Geneva Medical School, 1211 Geneva, Switzerland [2] Institute for Genetics and Genomics in Geneva (iGE3), University of Geneva, 1211 Geneva, Switzerland [3] Swiss Institute of Bioinformatics, 1211 Geneva, Switzerland.
Nature
|August 1, 2014
概括
研究人员通过分析基因表达变化,发现了71种可能导致结直肠癌 (CRC) 的新基因. 这些发现强调了 cis 调节效应在癌症发展中的重要性,并为CRC研究提供了新的目标.
科学领域:
- 基因组学就是基因组学.
- 癌症生物学 癌症生物学
- 分子瘤学分子瘤学
背景情况:
- 与蛋白质编码基因组改变相比,对瘤发生的研究较少.
- 了解这些影响对于全面了解癌症发展至关重要.
研究的目的:
- 调查结直肠癌 (CRC) 发展中的cis调节效应.
- 在CRC中识别新的癌症驱动基因和调控机制.
主要方法:
- 来自丹麦CRC患者的103个匹配瘤和正常结肠粘膜样本的RNA测序.
- 对等位基因特异性表达 (ASE) 的分析,以评估生殖系基因型对基因表达的影响.
- 在正常和瘤样本中识别表达量的特征位点 (eQTL).
主要成果:
- 发现了71个基因在CRC中具有过多的体质调节效应,表明潜在的驱动作用.
- 在正常和瘤样本中分别确定了1693个和948个eQTL.
- 发现36%的瘤eQTL是CRC特异性的,受转录因子和甲基化影响.
结论:
- 生殖系基因型显著影响瘤中的等位基因表达.
- 瘤特异性eQTL为较低的CRC GWAS P值而被丰富,并积累了更多的体质突变,表明潜在的生殖系衍生癌症驱动因素.
- 基因组和转录组数据的整合揭示了许多涉及CRC瘤发生的cis-regulatory变化.
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