同名突变经常在人类癌症中充当驱动突变
Fran Supek1, Belén Miñana2, Juan Valcárcel3
1EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation, Dr. Aiguader 88, 08003 Barcelona, Spain; Centre for Genomic Regulation, Universitat Pompeu Fabra, Barcelona 08003, Spain.
Cell
|March 18, 2014
概括
同名突变,以前被认为是"沉默的",通过影响基因拼接,显著促进人类癌症. 这些突变在瘤基因和瘤抑制剂中被选择,影响癌症的发展.
科学领域:
- 遗传学 是一个遗传学.
- 癌症生物学 癌症生物学
- 分子生物学分子生物学
背景情况:
- 同名突变改变了DNA序列,而没有改变蛋白质序列.
- 这些突变通常被认为是中性或中性的.
- 这是一个沉默的,无声的世界.
- 在它们的功能影响.
研究的目的:
- 研究同名突变在人类癌症中的作用.
- 为了确定同义突变是否在癌症基因中受到选择.
- 探索选择同名突变的功能后果.
主要方法:
- 对瘤基因和瘤抑制基因同名突变的分析.
- 癌症类型特定的选择分析.
- 对外标拼接监管动机的调查.
- 在3'未翻译区域 (UTR) 中对突变的评估.
主要成果:
- 同名突变在人类癌症中经常被选择,具有癌症类型特异性.
- 选择的同名突变经常改变拼接调节动机,影响基因拼接.
- 在TP53中反复出现的同名突变使拼接部位失活.
- 据估计,在瘤基因中选择的单核酸变化的6-8%是同义突变.
- 剂量敏感的瘤基因在其3' UTRs中显示了选择性的突变.
结论:
- 同名突变并不总是沉默,在癌症的发展中起着重要作用.
- 由同名突变驱动的拼接变化是瘤发生的一个关键机制.
- 同名突变的影响取决于上下文,在瘤基因和瘤抑制剂之间有所不同.
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