插入和删除针对人类癌症的基因
Marcin Imielinski1, Guangwu Guo2, Matthew Meyerson3
1Department of Pathology and Laboratory Medicine, Englander Institute for Precision Medicine, Institute for Computational Biomedicine, and Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10065, USA; New York Genome Center, New York, NY 10013, USA.
Cell
|January 17, 2017
概括
癌细胞在基因中表现出独特的突变模式, 研究人员在各种癌症中发现了分泌细胞系基因中的新兴热点,揭示了细胞类型和癌症发展之间的联系.
科学领域:
- 基因组学
- 癌症生物学
- 分子瘤学
背景情况:
- 特定类型的细胞分泌器官功能至关重要的蛋白质,如肺部的表面活性蛋白,肝脏的白蛋白和胃中的脂酶.
- 之前的肺腺癌基因组研究在表面活性蛋白基因中发现了非编码体位突变热点和内基因热点.
研究的目的:
- 调查各种固体癌症中高表达基因的非编码区域的存在和特征.
- 确定细胞系与癌症发展之间的潜在突变过程.
主要方法:
- 肺腺癌的全基因组测序分析.
- 将结果推断到其他固体癌症,包括肝脏,胃和甲状腺癌.
- 分析与indel热点相关的序列背景和染色质状态.
主要成果:
- 在界定基因的非编码区域 (例如,ALB,LIPF,TG) 发现了复发性,瘤类型特异性的内核热点.
- 这些内核热点在AATAATDDNA图案中显著丰富.
- 包括H3K27ac和H3K36me3在内的特定染色体背景与这些突变热点有关.
结论:
- 一个以前未知的突变过程针对癌症中高度表达的基因的非编码区域.
- 这一过程将细胞分泌系与特定的癌症突变场景联系起来.
- 这些发现提供了由细胞身份驱动的癌症发展机制的见解.
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