人类癌症中"基"突变的扩大
Benjamin A Nacev1,2, Lijuan Feng2, John D Bagert3
1Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nature
|March 22, 2019
概括
大约4%的各种癌症中发现了体质基因突变,影响了关键的蛋白质区域. 通过改变染色体功能,这些核心基因组突变可能导致癌症.
科学领域:
- 癌症生物学
- 表观遗传学
- 分子生物学
背景情况:
- 表观遗传路径的突变是癌症的关键驱动因素.
- 在特定的癌症中已知基因突变,特别是基因 H3 N-终端尾巴中的基因突变,影响多抑制复合体 (PRC1 和 PRC2).
- 基因突变在各种癌症类型中的更广泛的患病率和功能影响仍然在很大程度上未被探索.
研究的目的:
- 研究不同类型的人类瘤体质基因突变的发病率和位置.
- 识别受突变影响的关键基因组区域和残留物.
- 假设这些突变对染色体调节和癌症发展的功能后果.
主要方法:
- 对各种瘤类型体质基因突变的综合数据集的分析.
- 鉴定基因蛋白内突变位置,包括N端尾和球状域.
- 与已知的功能域和同类酵母突变相比较已知突变.
主要成果:
- 在大约4%的各种瘤中发现了体质基因突变.
- 突变影响N端尾和球状域的四个核心基因素 (H2A,H2B,H3,H4).
- 突变发生在关键的翻译后修改部位附近,在H2A/H2B的酸性补丁中,以及在H2B-H4接口上,一些同类酵母突变会影响SWI/SNF功能.
结论:
- 人体基因突变比以前更为普遍和多样化.
- 这些突变发生在基因组的功能关键区域,这表明基因组在瘤发生过程中起着重要作用.
- 这些发现为未来研究基因突变在癌症和染色体调节中的作用提供了宝贵的资源.
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