在人类黑色素瘤中高度复发的TERT促进子突变
Franklin W Huang1, Eran Hodis, Mary Jue Xu
1Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
概括
在71%的黑色素瘤中发现了2种新型突变的端粒酶逆转录酶 (TERT) 促进体,增加了基因活性. 这些发现表明,基因调节区域的突变是癌症发展的重要机制.
科学领域:
- 在瘤学瘤学.
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 人类癌症基因组的系统测序主要确定了蛋白质编码基因的突变,不太关注基因调节区域.
- 端粒酶逆转录酶 (TERT) 基因对端粒维护至关重要,并与癌症有关.
- 了解调节区域的突变是揭示新型癌症机制的关键.
研究的目的:
- 在人类癌症中识别和表征TERT基因促进者的突变.
- 研究这些突变对TERT基因转录的功能影响.
- 为了确定这些突变在各种癌症类型中的患病率.
主要方法:
- 黑色素瘤样本的全基因组测序.
- 报告员测试评估突变对TERT促进体活动的影响.
- 查各种癌症细胞系的鉴定突变.
主要成果:
- 在TERT基因的核心促进体中发现了两种不同的突变,在71%的黑色素瘤中发生.
- 这些突变为E-twenty-six (ETS) 转录因子创造了新的结合点.
- 记者测试表明,转录活性由突变的TERT促进体增加两到四倍.
- 在16%的不同癌症细胞系中发现了相同的突变,在膀和肝细胞癌中频率显著.
结论:
- 在TERT促进者的体质突变是黑色素瘤和其他癌症的频繁事件.
- 这些突变增强了TERT基因转录,可能有助于瘤发生.
- 基因调节区域的突变代表了癌症发展中的重要,以前被低估的机制.
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