在白血病中,广泛的内基多基化会使瘤抑制基因失活
Shih-Han Lee1, Irtisha Singh2,3, Sarah Tisdale1
1Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nature
|August 29, 2018
概括
在慢性淋巴细胞白血病 (CLL) 中,异常的信使RNA (mRNA) 处理,特别是内基多基化,会使瘤抑制基因失活. 这种mRNA事件在推动癌症进展方面比基因突变更常见.
科学领域:
- 分子生物学
- 癌症基因组学
- 转录组学
背景情况:
- DNA突变已成为癌症发展的驱动因素.
- 在癌症中模仿基因变化的RNA事件的作用仍在研究中.
研究的目的:
- 调查癌症上调的mRNA事件是否可以功能性地复制遗传变化.
- 探索慢性淋巴细胞白血病 (CLL) 中的内基多化发生率和影响.
主要方法:
- 在59名CLL患者的正常和恶性B细胞上进行了RNA测序和3'- end测序.
- 分析的重点是识别上调的mRNA事件,特别是那些由内基多基化引起的事件.
主要成果:
- 在初级CLL细胞中发现了因内部多基化而导致的截断mRNA和蛋白质的广泛上调.
- 这些异常mRNA事件影响了330个复发基因,主要是具有瘤抑制功能的基因.
- 截断的蛋白质经常失去抑制瘤的功能或获得致癌性质,影响DICER,FOXN3,CARD11,MGA和CHST11等基因.
结论:
- 异常的mRNA处理,特别是内基多化,是CLL中瘤抑制基因失活的更普遍的机制,而不是遗传事件.
- 在白血病和固体瘤的DNA突变中,通过内基多基解激活的新型候选瘤抑制基因.
- 这些发现突显了分析基因组数据之外的mRNA事件的必要性,以全面诊断癌症并了解病变.
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