癌的系统测序揭示了基因组修饰基因的失活
Gillian L Dalgliesh1, Kyle Furge, Chris Greenman
1Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
Nature
|January 8, 2010
概括
研究人员在清细胞细胞癌 (ccRCC) 中发现了新的基因突变,这是一种常见的癌. 这些突变影响了参与基因组蛋白修饰的基因,揭示了超越VHL基因突变的显著遗传多样性.
科学领域:
- 遗传学 是一个遗传学.
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 清细胞细胞癌 (ccRCC) 是成年人中最常见的癌.
- 大多数ccRCC病例都在VHL基因中表现出失活突变.
- 已知癌症基因的体质突变在ccRCC中不常见.
研究的目的:
- 为了进一步阐明ccRCC的遗传景观.
- 确定涉及ccRCC发展的新基因和途径.
主要方法:
- 在3,544个蛋白质编码基因中对101个ccRCC病例进行了测序.
- 身体突变的识别和分析.
主要成果:
- 发现了SETD2 (基因组H3 lysine 36甲基转移酶) 和JARID1C/KDM5C (基因组H3 lysine 4脱甲基酶) 中的非活化突变.
- 在UTX/KMD6A (希 H3氨酸27脱甲基酶) 中确认了突变.
- 在没有VHL突变和其他潜在癌症基因的ccRCC病例中确定了NF2突变.
结论:
- 染色体修饰机械组件中的突变在ccRCC病原发生过程中发挥作用.
- 在ccRCC中存在显著的遗传异质性,超越了VHL基因突变.
- 系统的遗传选对于全面了解ccRCC体质遗传结构至关重要.
相关概念视频
Epigenetic Regulation
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
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Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Spreading of Chromatin Modifications
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
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